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Angiotensin‑converting enzyme 2 expression in human tumors: Implications for prognosis and therapy (Review)

  • Authors:
    • Theodoros Rizopoulos
    • Martha Assimakopoulou
  • View Affiliations / Copyright

    Affiliations: Department of Anatomy, Histology and Embryology, School of Medicine, University of Patras, 26504 Patras, Greece
    Copyright: © Rizopoulos et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 101
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    Published online on: June 25, 2025
       https://doi.org/10.3892/or.2025.8934
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Abstract

Angiotensin‑converting enzyme 2 (ACE2) is one of the components of the renin‑angiotensin system. The differential expression of ACE2 is associated with carcinogenesis. ACE2 expression is altered in certain types of tumor following severe acute respiratory syndrome coronavirus 2 infection. The present review aimed to summarize the role of ACE2 expression in the pathogenesis of tumors of the central nervous and endocrine system, respiratory tract, breast, gastrointestinal tract, genitourinary system, skin and bone, as well as hematological malignancies. ACE2 should be further evaluated in the pathogenesis of various types of human tumor to determine its diagnostic and prognostic value. Additionally, the present review summarizes the potential of ACE2 as a novel therapeutic target for cancer. However, the role of ACE2 expression as a novel chemotherapeutic tool for various human malignancies remains to be fully elucidated.
View Figures

Figure 1

ACE2 structure and function. The ACE2
gene, which shares 42% sequence homology with ACE, is located on
chromosome Xp22.2, and the 805-amino-acid-long protein that it
encodes regulates the renin-angiotensin system by cleaving
angiotensin I to angiotensin 1–9, and angiotensin II peptide to
angiotensin 1–7, which promotes vasodilation and inhibits
proliferation and hypertrophy. ACE2, angiotensin-converting enzyme
2.

Figure 2

Human organ/tissue specific
expression of ACE2. (A) Placenta, kidneys, lung, heart, testis,
breast, ovaries, corpus luteum, gallbladder, liver and
gastrointestinal tract exhibit high ACE2 expression, with the
greatest density of expression observed across the testis and small
intestine. By contrast, the spleen, brain, bone marrow, endocrine
glands and skin demonstrate low ACE2 expression. ACE2 expression in
the urothelium, lymphatic tissues, endometrium and endocervix is
low to undetectable. (B) ACE2 expression in the heart is involved
in cardiac remodeling and conductance, whereas ACE2 expression in
the kidney is involved in the pathogenesis of renal damage. In the
lung, ACE2 expression protects against severe acute lung failure.
ACE2, angiotensin-converting enzyme 2.
View References

1 

Shang J, Ye G, Shi K, Wan Y, Luo C, Aihara H, Geng Q, Auerbach A and Li F: Structural basis of receptor recognition by SARS-CoV-2. Nature. 581:221–224. 2020. View Article : Google Scholar : PubMed/NCBI

2 

Gupta A, Madhavan MV, Sehgal K, Nair N, Mahajan S, Sehrawat TS, Bikdeli B, Ahluwalia N, Ausiello JC, Wan EY, et al: Extrapulmonary manifestations of COVID-19. Nat Med. 26:1017–1032. 2020. View Article : Google Scholar : PubMed/NCBI

3 

Danilczyk U, Eriksson U, Crackower MA and Penninger JM: A story of two ACEs. J Mol Med (Berl). 81:227–234. 2003. View Article : Google Scholar : PubMed/NCBI

4 

Santos RA, Campagnole-Santos MJ and Andrade SP: Angiotensin-(1–7): An update. Regul Pept. 91:45–62. 2000. View Article : Google Scholar : PubMed/NCBI

5 

Ferrario CM, Trask AJ and Jessup JA: Advances in biochemical and functional roles of angiotensin-converting enzyme 2 and angiotensin-(1–7) in regulation of cardiovascular function. Am J Physiol Heart Circ Physiol. 289:H2281–2290. 2005. View Article : Google Scholar : PubMed/NCBI

6 

Yang Z, Macdonald-Dunlop E, Chen J, Zhai R, Li T, Richmond A, Klarić L, Pirastu N, Ning Z, Zheng C, et al: Genetic landscape of the ACE2 coronavirus receptor. Circulation. 145:1398–1411. 2022. View Article : Google Scholar : PubMed/NCBI

7 

Hamming I, Cooper ME, Haagmans BL, Hooper NM, Korstanje R, Osterhaus AD, Timens W, Turner AJ, Navis G and van Goor H: The emerging role of ACE2 in physiology and disease. J Pathol. 12:1–11. 2007. View Article : Google Scholar

8 

Crackower MA, Sarao R, Oudit GY, Yagil C, Kozieradzki I, Scanga SE, Oliveira-dos-Santos AJ, da Costa J, Zhang L, Pei Y, et al: Angiotensin-converting enzyme 2 is an essential regulator of heart function. Nature. 417:822–828. 2002. View Article : Google Scholar : PubMed/NCBI

9 

Donoghue M, Wakimoto H, Maguire CT, Acton S, Hales P, Stagliano N, Fairchild-Huntress V, Xu J, Lorenz JN, Kadambi V, et al: Heart block, ventricular tachycardia, and sudden death in ACE2 transgenic mice with downregulated connexins. J Mol Cell Cardiol. 35:1043–1053. 2003. View Article : Google Scholar : PubMed/NCBI

10 

Chen QL, Li JQ, Xiang ZD, Lang Y, Guo GJ and Liu ZH: Localization of cell receptor-related genes of SARS-CoV-2 in the kidney through single-cell transcriptome analysis. Kidney Dis (Basel). 6:258–270. 2020. View Article : Google Scholar : PubMed/NCBI

11 

Lely AT, Hamming I, van Goor H and Navis GJ: Renal ACE2 expression in human kidney disease. J Pathol. 204:587–593. 2004. View Article : Google Scholar : PubMed/NCBI

12 

Imai Y, Kuba K, Rao S, Huan Y, Guo F, Guan B, Yang P, Sarao R, Wada T, Leong-Poi H, et al: Angiotensin-converting enzyme 2 protects from severe acute lung failure. Nature. 436:112–116. 2005. View Article : Google Scholar : PubMed/NCBI

13 

Fu J, Zhou B, Zhang L, Balaji KS, Wei C, Liu X, Chen H, Peng J and Fu J: Expressions and significances of the angiotensin-converting enzyme 2 gene, the receptor of SARS-CoV-2 for COVID-19. Mol Biol Rep. 47:4383–4392. 2020. View Article : Google Scholar : PubMed/NCBI

14 

Meiners J, Jansen K, Gorbokon N, Büscheck F, Luebke AM, Kluth M, Hube-Magg C, Höflmayer D, Weidemann S, Fraune C, et al: Angiotensin-converting enzyme 2 protein is overexpressed in a wide range of human tumour types: A systematic tissue microarray study on >15,000 tumours. Biomedicines. 9:18312021. View Article : Google Scholar : PubMed/NCBI

15 

Mahalingam R, Dharmalingam P, Santhanam A, Kotla S, Davuluri G, Karmouty-Quintana H, Ashrith G and Thandavarayan RA: Single-cell RNA sequencing analysis of SARS-CoV-2 entry receptors in human organoids. J Cell Physiol. 236:2950–2958. 2021. View Article : Google Scholar : PubMed/NCBI

16 

Hikmet F, Méar L, Edvinsson Å, Micke P, Uhlén M and Lindskog C: The protein expression profile of ACE2 in human tissues. Mol Syst Biol. 16:e96102020. View Article : Google Scholar : PubMed/NCBI

17 

Han T, Kang J, Li G, Ge J and Gu J: Analysis of 2019-nCoV receptor ACE2 expression in different tissues and its significance study. Ann Transl Med. 8:10772020. View Article : Google Scholar : PubMed/NCBI

18 

Cui Y, Chen F, Gao J, Lei M, Wang D, Jin X, Guo Y, Shan L and Chen X: Comprehensive landscape of the renin-angiotensin system in Pan-cancer: A potential downstream mediated mechanism of SARS-CoV-2. Int J Biol Sci. 7:3795–3817. 2021. View Article : Google Scholar : PubMed/NCBI

19 

Song J, Han J, Liu F, Chen X, Qian S, Wang Y, Jia Z, Duan X, Zhang X and Zhu J: Systematic analysis of coronavirus disease 2019 (COVID-19) receptor ACE2 in malignant tumors: Pan-cancer analysis. Front Mol Biosci. 7:5694142020. View Article : Google Scholar : PubMed/NCBI

20 

Zhang L, Han X and Shi Y: Comparative analysis of SARS-CoV-2 receptor ACE2 expression in multiple solid tumors and matched non-diseased tissues. Infect Genet Evol. 85:1044282020. View Article : Google Scholar : PubMed/NCBI

21 

Li MY, Li L, Zhang Y and Wang XS: Expression of the SARS-CoV-2 cell receptor gene ACE2 in a wide variety of human tissues. Infect Dis Poverty. 9:452020. View Article : Google Scholar : PubMed/NCBI

22 

Qi J, Zhou Y, Hua J, Zhang L, Bian J, Liu B, Zhao Z and Jin S: The scRNA-seq expression profiling of the receptor ACE2 and the cellular protease TMPRSS2 reveals human organs susceptible to SARS-CoV-2 infection. Int J Environ Res Public Health. 18:2842021. View Article : Google Scholar : PubMed/NCBI

23 

Qi F, Qian S, Zhang S and Zhang Z: Single cell RNA sequencing of 13 human tissues identify cell types and receptors of human coronaviruses. Biochem Biophys Res Commun. 526:135–140. 2020. View Article : Google Scholar : PubMed/NCBI

24 

Li S, Han J, Zhang A, Han Y, Chen M, Liu Z, Shao M and Cao W: Exploring the demographics and clinical characteristics related to the expression of angiotensin-converting enzyme 2, a receptor of SARS-CoV-2. Front Med (Lausanne). 7:5302020. View Article : Google Scholar : PubMed/NCBI

25 

Viveiros A, Gheblawi M, Aujla PK, Sosnowski DK, Seubert JM, Kassiri Z and Oudit GY: Sex- and age-specific regulation of ACE2: Insights into severe COVID-19 susceptibility. J Mol Cell Cardiol. 164:13–16. 2022. View Article : Google Scholar : PubMed/NCBI

26 

Schurink B, Roos E, Vos W, Breur M, van der Valk P and Bugiani M: ACE2 protein expression during childhood, adolescence, and early adulthood. Pediatr Dev Pathol. 25:404–408. 2022. View Article : Google Scholar : PubMed/NCBI

27 

Ravaioli S, Tebaldi M, Fonzi E, Angeli D, Mazza M, Nicolini F, Lucchesi A, Fanini F, Pirini F, Tumedei MM, et al: ACE2 and TMPRSS2 potential involvement in genetic susceptibility to SARS-COV-2 in cancer patients. Cell Transplant. 29:09636897209687492020. View Article : Google Scholar : PubMed/NCBI

28 

Chakladar J, Shende N, Li WT, Rajasekaran M, Chang EY and Ongkeko WM: Smoking-mediated upregulation of the androgen pathway leads to increased SARS-CoV-2 susceptibility. Int J Mol Sci. 21:36272020. View Article : Google Scholar : PubMed/NCBI

29 

Goren A, Wambier CG, Herrera S, McCoy J, Vaño-Galván S, Gioia F, Comeche B, Ron R, Serrano-Villar S, Ramos PM, et al: Anti-androgens may protect against severe COVID-19 outcomes: Results from a prospective cohort study of 77 hospitalized men. J Eur Acad Dermatol Venereol. 35:e13–e15. 2021. View Article : Google Scholar : PubMed/NCBI

30 

Bhardwaj V, Dela Cruz M, Subramanyam D, Kumar R, Markan S, Parker B and Roy HK: Exercise-induced myokines downregulates the ACE2 level in bronchial epithelial cells: Implications for SARS-CoV-2 prevention. PLoS One. 17:e02713032022. View Article : Google Scholar : PubMed/NCBI

31 

Xie J, Huang QF, Zhang Z, Dong Y, Xu H, Cao Y, Sheng CS, Li Y, Wang C, Wang X and Wang JG: Angiotensin-converting enzyme 2 in human plasma and lung tissue. Blood Press. 32:6–15. 2023. View Article : Google Scholar : PubMed/NCBI

32 

Rao S, Lau A and So HC: Exploring diseases/traits and blood proteins causally related to expression of ACE2, the putative receptor of SARS-CoV-2: A mendelian randomization analysis highlights tentative relevance of diabetes-related traits. Diabetes Care. 43:1416–1426. 2020. View Article : Google Scholar : PubMed/NCBI

33 

Facchiano A, Facchiano F and Facchiano A: An investigation into the molecular basis of cancer comorbidities in coronavirus infection. FEBS Open Bio. 10:2363–2374. 2020. View Article : Google Scholar : PubMed/NCBI

34 

Gheblawi M, Wang K, Viveiros A, Nguyen Q, Zhong JC, Turner AJ, Raizada MK, Grant MB and Oudit GY: Angiotensin-converting enzyme 2: SARS-CoV-2 receptor and regulator of the renin-angiotensin system: Celebrating the 20th anniversary of the discovery of ACE2. Circ Res. 126:1456–1474. 2020. View Article : Google Scholar : PubMed/NCBI

35 

Leung JM, Yang CX, Tam A, Shaipanich T, Hackett TL, Singhera GK, Dorscheid DR and Sin DD: ACE-2 expression in the small airway epithelia of smokers and COPD patients: Implications for COVID-19. Eur Respir J. 55:20006882020. View Article : Google Scholar : PubMed/NCBI

36 

Kornilov SA, Lucas I, Jade K, Dai CL, Lovejoy JC and Magis AT: Plasma levels of soluble ACE2are associated with sex, Metabolic Syndrome, and its biomarkers in a large cohort, pointing to a possible mechanism for increased severity in COVID-19. Crit Care. 24:4522020. View Article : Google Scholar : PubMed/NCBI

37 

Chirinos JA, Cohen JB, Zhao L, Hanff T, Sweitzer N, Fang J, Corrales-Medina V, Anmar R, Morley M, Zamani P, et al: Clinical and proteomic correlates of plasma ACE2 (Angiotensin-Converting Enzyme 2) in human heart failure. Hypertension. 76:1526–1536. 2020. View Article : Google Scholar : PubMed/NCBI

38 

Radzikowska U, Ding M, Tan G, Zhakparov D, Peng Y, Wawrzyniak P, Wang M, Li S, Morita H, Altunbulakli C, et al: Distribution of ACE2, CD147, CD26, and other SARS-CoV-2 associated molecules in tissues and immune cells in health and in asthma, COPD, obesity, hypertension, and COVID-19 risk factors. Allergy. 75:2829–2845. 2020. View Article : Google Scholar : PubMed/NCBI

39 

Dhawale VS, Amara VR, Karpe PA, Malek V, Patel D and Tikoo K: Activation of angiotensin-converting enzyme 2 (ACE2) attenuates allergic airway inflammation in rat asthma model. Toxicol Appl Pharmacol. 306:17–26. 2016. View Article : Google Scholar : PubMed/NCBI

40 

Ye R and Liu Z: ACE2 exhibits protective effects against LPS-induced acute lung injury in mice by inhibiting the LPS-TLR4 pathway. Exp Mol Pathol. 113:1043502020. View Article : Google Scholar : PubMed/NCBI

41 

Clarke NE, Belyaev ND, Lambert DW and Turner AJ: Epigenetic regulation of angiotensin-converting enzyme 2 (ACE2) by SIRT1 under conditions of cell energy stress. Clin Sci (Lond). 126:507–516. 2014. View Article : Google Scholar : PubMed/NCBI

42 

Li Y, Xu Q, Ma L, Wu D, Gao J, Chen G and Li H: Systematic profiling of ACE2 expression in diverse physiological and pathological conditions for COVID-19/SARS-CoV-2. J Cell Mol Med. 24:9478–9482. 2020. View Article : Google Scholar : PubMed/NCBI

43 

Feng H, Wei X, Pang L, Wu Y, Hu B, Ruan Y, Liu Z, Liu J and Wang T: Prognostic and immunological value of angiotensin-converting enzyme 2 in pan-cancer. Front Mol Biosci. 7:1892020. View Article : Google Scholar : PubMed/NCBI

44 

Chai P, Yu J, Ge S, Jia R and Fan X: Genetic alteration, RNA expression, and DNA methylation profiling of coronavirus disease 2019 (COVID-19) receptor ACE2 in malignancies: A pan-cancer analysis. J Hematol Oncol. 13:432020. View Article : Google Scholar : PubMed/NCBI

45 

Li H, Xie L, Chen L, Zhang L, Han Y, Yan Z and Guo X: Genomic, epigenomic, and immune subtype analysis of CTSL/B and SARS-CoV-2 receptor ACE2 in pan-cancer. Aging. 12:22370–22389. 2020.PubMed/NCBI

46 

Zhao K, Zhang D, Xu X, Wang S, Liu Z, Ren X, Zhang X, Lu Z, Ren S and Qin C: Exploring the potential mechanisms of impairment on genitourinary system associated with coronavirus disease 2019 infection: Bioinformatics and molecular simulation analyses. Asian J Urol. 10:344–355. 2023. View Article : Google Scholar : PubMed/NCBI

47 

He J, Yang X and Wang H: Construction of a risk map to understand the vulnerability of various types of cancer patients to COVID-19 infection. MedComm (2020). 2:69–81. 2021. View Article : Google Scholar : PubMed/NCBI

48 

de Paula Gonzaga ALAC, Palmeira VA, Ribeiro TFS, Costa LB, de Sá, Rodrigues KE and Simões-E-Silva AC: ACE2/Angiotensin-(1–7)/Mas receptor axis in human cancer: Potential role for pediatric tumors. Curr Drug Targets. 21:892–901. 2020. View Article : Google Scholar : PubMed/NCBI

49 

Xu J, Fan J, Wu F, Huang Q, Guo M, Lv Z, Han J, Duan L, Hu G, Chen L, et al: The ACE2/Angiotensin-(1–7)/Mas receptor axis: Pleiotropic roles in cancer. Front Physiol. 8:2762017. View Article : Google Scholar : PubMed/NCBI

50 

Bujak-Gizycka B, Madej J, Bystrowska B, Toton-Zuranska J, Kus K, Kolton-Wroz M, Jawien J and Olszanecki R: Angiotensin 1–7 formation in breast tissue is attenuated in breast cancer-a study on the metabolism of angiotensinogen in breast cancer cell lines. J Physiol Pharmacol. 702019.doi: 10.26402/jpp.2019.4.02.

51 

Bernardi S, Zennaro C, Palmisano S, Velkoska E, Sabato N, Toffoli B, Giacomel G, Buri L, Zanconati F, Bellini G, et al: Characterization and significance of ACE2 and Mas receptor in human colon adenocarcinoma. J Renin Angiotensin Aldosterone Syst. 13:202–209. 2012. View Article : Google Scholar : PubMed/NCBI

52 

Zhang Z, Li L, Li M and Wang X: The SARS-CoV-2 host cell receptor ACE2 correlates positively with immunotherapy response and is a potential protective factor for cancer progression. Comput Struct Biotechnol J. 18:2438–2444. 2020. View Article : Google Scholar : PubMed/NCBI

53 

Song T, Choi CH, Kim MK, Kim ML, Yun BS and Seong SJ: The effect of angiotensin system inhibitors (angiotensin-converting enzyme inhibitors or angiotensin receptor blockers) on cancer recurrence and survival: A meta-analysis. Eur J Cancer Prev. 26:78–85. 2017. View Article : Google Scholar : PubMed/NCBI

54 

Harmer D, Gilbert M, Borman R and Clark KL: Quantitative mRNA expression profiling of ACE 2, a novel homologue of angiotensin converting enzyme. FEBS Lett. 532:107–110. 2022. View Article : Google Scholar : PubMed/NCBI

55 

Chen R, Wang K, Yu J, Howard D, French L, Chen Z, Wen C and Xu Z: The spatial and cell-type distribution of SARS-CoV-2 receptor ACE2 in the human and mouse brains. Front Neurol. 11:5730952021. View Article : Google Scholar : PubMed/NCBI

56 

Xia H and Lazartigues E: Angiotensin-converting enzyme 2 in the brain: Properties and future directions. J Neurochem. 107:1482–1494. 2008. View Article : Google Scholar : PubMed/NCBI

57 

Kase Y and Okano H: Expression of ACE2 and a viral virulence-regulating factor CCN family member 1 in human iPSC-derived neural cells: Implications for COVID-19-related CNS disorders. Inflamm Regen. 40:322020. View Article : Google Scholar : PubMed/NCBI

58 

Lukiw WJ, Pogue A and Hill JM: SARS-CoV-2 infectivity and neurological targets in the brain. Cell Mol Neurobiol. 42:217–224. 2022. View Article : Google Scholar : PubMed/NCBI

59 

Doobay MF, Talman LS, Obr TD, Tian X, Davisson RL and Lazartigues E: Differential expression of neuronal ACE2 in transgenic mice with overexpression of the brain renin-angiotensin system. Am J Physiol Regul Integr Comp Physiol. 292:R373–R381. 2007. View Article : Google Scholar : PubMed/NCBI

60 

Chen A, Zhao W, Li X, Sun G, Ma Z, Peng L, Shi Z, Li X and Yan J: Comprehensive oncogenic features of coronavirus receptors in glioblastoma multiforme. Front Immunol. 13:8407852022. View Article : Google Scholar : PubMed/NCBI

61 

Ren X, Wang S, Chen X, Wei X, Li G, Ren S, Zhang T, Zhang X, Lu Z, You Z, et al: Multiple expression assessments of ACE2 and TMPRSS2 SARS-CoV-2 entry molecules in the urinary tract and their associations with clinical manifestations of COVID-19. Infect Drug Resist. 13:3977–3990. 2020. View Article : Google Scholar : PubMed/NCBI

62 

Hamming I, Timens W, Bulthuis ML, Lely AT, Navis G and van Goor H: Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J Pathol. 203:631–637. 2004. View Article : Google Scholar : PubMed/NCBI

63 

Muhl L, He L, Sun Y, Andaloussi Mäe M, Pietilä R, Liu J, Genové G, Zhang L, Xie Y, Leptidis S, et al: The SARS-CoV-2 receptor ACE2 is expressed in mouse pericytes but not endothelial cells: Implications for COVID-19 vascular research. Stem Cell Reports. 17:1089–1104. 2022. View Article : Google Scholar : PubMed/NCBI

64 

Chen J, Zhao Y, Chen S, Wang J, Xiao X, Ma X, Penchikala M, Xia H, Lazartigues E, Zhao B and Chen Y: Neuronal over-expression of ACE2 protects brain from ischemia-induced damage. Neuropharmacology. 79:550–558. 2014. View Article : Google Scholar : PubMed/NCBI

65 

Qiao J, Li W, Bao J, Peng Q, Wen D, Wang J and Sun B: The expression of SARS-CoV-2 receptor ACE2 and CD147, and protease TMPRSS2 in human and mouse brain cells and mouse brain tissues. Biochem Biophys Res Commun. 533:867–871. 2020. View Article : Google Scholar : PubMed/NCBI

66 

Bielarz V, Willemart K, Avalosse N, De Swert K, Lotfi R, Lejeune N, Poulain F, Ninanne N, Gilloteaux J, Gillet N and Nicaise C: Susceptibility of neuroblastoma and glioblastoma cell lines to SARS-CoV-2 infection. Brain Res. 1758:1473442021. View Article : Google Scholar : PubMed/NCBI

67 

Vanhulle E, Stroobants J, Provinciael B, Camps A, Noppen S, Maes P and Vermeire K: SARS-CoV-2 Permissive glioblastoma cell line for high throughput antiviral screening. Antiviral Res. 203:1053422022. View Article : Google Scholar : PubMed/NCBI

68 

Bergsneider B, Bailey E, Ahmed Y, Gogineni N, Huntley D and Montano X: Analysis of SARS-CoV-2 infection associated cell entry proteins ACE2, CD147, PPIA, and PPIB in datasets from non SARS-CoV-2 infected neuroblastoma patients, as potential prognostic and infection biomarkers in neuroblastoma. Biochem Biophys Rep. 27:1010812021.PubMed/NCBI

69 

Kim K, Ko Y, Ko DS and Kim YH: Prognostic significance of COVID-19 receptor ACE2 and recommendation for antihypertensive drug in renal cell carcinoma. Biomed Res Int. 2020:20543762020. View Article : Google Scholar : PubMed/NCBI

70 

Wu B, Wang W, Wang H, Zou Q, Hu B, Ye L, Hu Y, Xie Y, Huang N, Lan Q, et al: Single-cell sequencing of glioblastoma reveals central nervous system susceptibility to SARS-CoV-2. Front Oncol. 10:5665992020. View Article : Google Scholar : PubMed/NCBI

71 

Lei J, Liu Y, Xie T, Yao G, Wang G, Diao B and Song J: Evidence for residual SARS-CoV-2 in glioblastoma tissue of a convalescent patient. Neuroreport. 32:771–775. 2021. View Article : Google Scholar : PubMed/NCBI

72 

Suarez-Meade P, Watanabe F, Ruiz-Garcia H, Rafferty SB, Moniz-Garcia D, Schiapparelli PV, Jentoft ME, Imitola J and Quinones-Hinojosa A: SARS-CoV2 entry factors are expressed in primary human glioblastoma and recapitulated in cerebral organoid models. Neurooncol. 161:67–76. 2023. View Article : Google Scholar : PubMed/NCBI

73 

Parolin M, Parisotto M, Zanchetta F, Sartorato P and De Menis E: Coronaviruses and endocrine system: A systematic review on evidences and shadows. Endocr Metab Immune Disord Drug Targets. 21:1242–1251. 2021. View Article : Google Scholar : PubMed/NCBI

74 

Gu WT, Zhou F, Xie WQ, Wang S, Yao H, Liu YT, Gao L and Wu ZB: A potential impact of SARS-CoV-2 on pituitary glands and pituitary neuroendocrine tumors. Endocrine. 72:340–348. 2021. View Article : Google Scholar : PubMed/NCBI

75 

Narayan SS, Lorenz K, Ukkat J, Hoang-Vu C and Trojanowicz B: Angiotensin converting enzymes ACE and ACE2 in thyroid cancer progression. Neoplasma. 67:402–409. 2020. View Article : Google Scholar : PubMed/NCBI

76 

An X, Lin W, Liu H, Zhong W, Zhang X, Zhu Y, Wang X, Li J and Sheng Q: SARS-CoV-2 host receptor ACE2 protein expression atlas in human gastrointestinal tract. Front Cell Dev Biol. 9:6598092021. View Article : Google Scholar : PubMed/NCBI

77 

Wu CT, Lidsky PV, Xiao Y, Lee IT, Cheng R, Nakayama T, Jiang S, Demeter J, Bevacqua RJ, Chang CA, et al: SARS-CoV-2 infects human pancreatic β cells and elicits β cell impairment. Cell Metab. 33:1565–1576.e5. 2021. View Article : Google Scholar : PubMed/NCBI

78 

Müller JA, Groß R, Conzelmann C, Krüger J, Merle U, Steinhart J, Weil T, Koepke L, Bozzo CP, Read C, et al: SARS-CoV-2 infects and replicates in cells of the human endocrine and exocrine pancreas. Nat Metab. 3:149–165. 2021. View Article : Google Scholar : PubMed/NCBI

79 

Fignani D, Licata G, Brusco N, Nigi L, Grieco GE, Marselli L, Overbergh L, Gysemans C, Colli ML, Marchetti P, et al: SARS-CoV-2 receptor angiotensin I-converting enzyme type 2 (ACE2) is expressed in human pancreatic β-cells and in the human pancreas microvasculature. Front Endocrinol (Lausanne). 11:5968982020. View Article : Google Scholar : PubMed/NCBI

80 

Kusmartseva I, Wu W, Syed F, Van Der Heide V, Jorgensen M, Joseph P, Tang X, Candelario-Jalil E, Yang C, Nick H, et al: Expression of SARS-CoV-2 entry factors in the pancreas of normal organ donors and individuals with COVID-19. Cell Metab. 32:1041–1051.e6. 2020. View Article : Google Scholar : PubMed/NCBI

81 

Coate KC, Cha J, Shrestha S, Wang W, Gonçalves LM, Almaça J, Kapp ME, Fasolino M, Morgan A, Dai C, et al: ARS-CoV-2 cell entry factors ACE2 and TMPRSS2 are expressed in the microvasculature and ducts of human pancreas but are not enriched in β cells. Cell Metab. 32:1028–1040.e4. 2020. View Article : Google Scholar : PubMed/NCBI

82 

Steenblock C, Richter S, Berger I, Barovic M, Schmid J, Schubert U, Jarzebska N, von Mässenhausen A, Linkermann A, Schürmann A, et al: Viral infiltration of pancreatic islets in patients with COVID-19. Nat Commun. 12:35342021. View Article : Google Scholar : PubMed/NCBI

83 

Qadir MMF, Bhondeley M, Beatty W, Gaupp DD, Doyle-Meyers LA, Fischer T, Bandyopadhyay I, Blair RV, Bohm R, Rappaport J, et al: SARS-CoV-2 infection of the pancreas promotes thrombofibrosis and is associated with new-onset diabetes. JCI Insight. 6:e1515512021. View Article : Google Scholar : PubMed/NCBI

84 

Pedersen KB, Chhabra KH, Nguyen VK, Xia H and Lazartigues E: The transcription factor HNF1α induces expression of angiotensin-converting enzyme 2 (ACE2) in pancreatic islets from evolutionarily conserved promoter motifs. Biochim Biophys Acta. 1829:1225–1235. 2013. View Article : Google Scholar : PubMed/NCBI

85 

Zhou L, Zhang R, Yao W, Wang J, Qian A, Qiao M, Zhang Y and Yuan Y: Decreased expression of angiotensin-converting enzyme 2 in pancreatic ductal adenocarcinoma is associated with tumor progression. Tohoku J Exp Med. 217:123–131. 2009. View Article : Google Scholar : PubMed/NCBI

86 

Huang X, He C, Hua X, Kan A, Sun S, Wang J and Li S: Bioinformatic analysis of correlation between immune infiltration and COVID-19 in cancer patients. Int J Biol Sci. 16:2464–2476. 2020. View Article : Google Scholar : PubMed/NCBI

87 

Zhou L, Zhang R, Zhang L, Yao W, Li J and Yuan Y: Angiotensin-converting enzyme 2 acts as a potential molecular target for pancreatic cancer therapy. Cancer Lett. 307:18–25. 2011. View Article : Google Scholar : PubMed/NCBI

88 

Lau ST and Leung PS: Role of the RAS in pancreatic cancer. Curr Cancer Drug Targets. 11:412–420. 2011. View Article : Google Scholar : PubMed/NCBI

89 

Donoghue M, Hsieh F, Baronas E, Godbout K, Gosselin M, Stagliano N, Donovan M, Woolf B, Robison K, Jeyaseelan R, et al: A novel angiotensin-converting enzyme-related carboxypeptidase (ACE2) converts angiotensin I to angiotensin 1–9. Circ Res. 87:E1–E9. 2000. View Article : Google Scholar : PubMed/NCBI

90 

Burrell LM, Risvanis J, Kubota E, Dean RG, MacDonald PS, Lu S, Tikellis C, Grant SL, Lew RA, Smith AI, et al: Myocardial infarction increases ACE2 expression in rat and humans. Eur Heart J. 26:369–375. 2005. View Article : Google Scholar : PubMed/NCBI

91 

Patel VB, Zhong JC, Grant MB and Oudit GY: Role of the ACE2/Angiotensin 1–7 axis of the renin-angiotensin system in heart failure. Circ Res. 118:1313–1326. 2016. View Article : Google Scholar : PubMed/NCBI

92 

Basu R, Poglitsch M, Yogasundaram H, Thomas J, Rowe BH and Oudit GY: Roles of angiotensin peptides and recombinant human ACE2 in heart failure. J Am Coll Cardiol. 69:805–819. 2017. View Article : Google Scholar : PubMed/NCBI

93 

Shen M, Hu M, Fedak PWM, Oudit GY and Kassiri Z: Cell-specific functions of ADAM17 regulate the progression of thoracic aortic aneurysm. Circ Res. 123:372–388. 2018. View Article : Google Scholar : PubMed/NCBI

94 

Epelman S, Tang WH, Chen SY, Van Lente F, Francis GS and Sen S: Detection of soluble angiotensin-converting enzyme 2 in heart failure: Insights into the endogenous counter-regulatory pathway of the renin-angiotensin-aldosterone system. J Am Coll Cardiol. 52:750–754. 2008. View Article : Google Scholar : PubMed/NCBI

95 

Madjid M, Safavi-Naeini P, Solomon SD and Vardeny O: Potential effects of coronaviruses on the cardiovascular system: A review. JAMA Cardiol. 5:831–840. 2020. View Article : Google Scholar : PubMed/NCBI

96 

Chung MK, Zidar DA, Bristow MR, Cameron SJ, Chan T, Harding CV III, Kwon DH, Singh T, Tilton JC, Tsai EJ, et al: COVID-19 and cardiovascular disease: From bench to bedside. Circ Res. 128:1214–1236. 2021. View Article : Google Scholar : PubMed/NCBI

97 

Brumback BD, Dmytrenko O, Robinson AN, Bailey AL, Ma P, Liu J, Hicks SC, Ng S, Li G, Zhang DM, et al: Human cardiac pericytes are susceptible to SARS-CoV-2 infection. JACC Basic Transl Sci. 8:109–120. 2023. View Article : Google Scholar : PubMed/NCBI

98 

Zou X, Chen K, Zou J, Han P, Hao J and Han Z: Single-cell RNA-seq data analysis on the receptor ACE2 expression reveals the potential risk of different human organs vulnerable to 2019-nCoV infection. Front Med. 14:185–192. 2020. View Article : Google Scholar : PubMed/NCBI

99 

Zhou Y, Huang Y, Song X, Guo X, Pang J, Wang J, Zhang S and Wang C: Single-cell transcriptional profile of ACE2 in healthy and failing human hearts. Sci China Life Sci. 64:652–655. 2021. View Article : Google Scholar : PubMed/NCBI

100 

Klingenstein M, Klingenstein S, Neckel PH, Mack AF, Wagner AP, Kleger A, Liebau S and Milazzo A: Evidence of SARS-CoV2 entry protein ACE2 in the human nose and olfactory bulb. Cells Tissues Organs. 209:155–164. 2020. View Article : Google Scholar : PubMed/NCBI

101 

Deprez M, Zaragosi LE, Truchi M, Becavin C, Ruiz García S, Arguel MJ, Plaisant M, Magnone V, Lebrigand K, Abelanet S, et al: A Single-cell atlas of the human healthy airways. Am J Respir Crit Care Med. 202:1636–1645. 2020. View Article : Google Scholar : PubMed/NCBI

102 

Sungnak W, Huang N, Bécavin C, Berg M, Queen R, Litvinukova M, Talavera-López C, Maatz H, Reichart D, Sampaziotis F, et al: HCA lung biological network. SARS-CoV-2 entry factors are highly expressed in nasal epithelial cells together with innate immune genes. Nat Med. 26:681–687. 2020. View Article : Google Scholar : PubMed/NCBI

103 

Lee IT, Nakayama T, Wu CT, Goltsev Y, Jiang S, Gall PA, Liao CK, Shih LC, Schürch CM, McIlwain DR, et al: ACE2 localizes to the respiratory cilia and is not increased by ACE inhibitors or ARBs. Nat Commun. 11:54532020. View Article : Google Scholar : PubMed/NCBI

104 

Bilinska K, Jakubowska P, Von Bartheld CS and Butowt R: Expression of the SARS-CoV-2 entry proteins, ACE2 and TMPRSS2, in cells of the olfactory epithelium: Identification of cell types and trends with age. ACS Chem Neurosci. 11:1555–1562. 2020. View Article : Google Scholar : PubMed/NCBI

105 

Xu H, Zhong L, Deng J, Peng J, Dan H, Zeng X, Li T and Chen Q: High expression of ACE2 receptor of 2019-nCoV on the epithelial cells of oral mucosa. Int J Oral Sci. 12:82020. View Article : Google Scholar : PubMed/NCBI

106 

Sapkota D, Sharma S, Søland TM, Braz-Silva PH and Teh MT: Expression profile of SARS-CoV-2 cellular entry proteins in normal oral mucosa and oral squamous cell carcinoma. Clin Exp Dent Res. 8:117–122. 2022. View Article : Google Scholar : PubMed/NCBI

107 

Sivasakthivel S, Ramani P and Poothakulath Krishnan R: Systematic review and Meta-analysis on angiotensin converting enzyme 2 in head and neck region. Cureus. 15:e336732023.PubMed/NCBI

108 

de Carvalho Fraga CA, Farias LC, Jones KM, Batista de Paula AM and Guimaraes ALS: Angiotensin-converting enzymes (ACE and ACE2) as potential targets for malignant epithelial neoplasia: Review and bioinformatics analyses focused in oral squamous cell carcinoma. Protein Pept Lett. 24:784–792. 2017. View Article : Google Scholar : PubMed/NCBI

109 

Hinsley EE, de Oliveira CE, Hunt S, Coletta RD and Lambert DW: Angiotensin 1–7 inhibits angiotensin II-stimulated head and neck cancer progression. Eur J Oral Sci. 125:247–257. 2017. View Article : Google Scholar : PubMed/NCBI

110 

Lin YT, Wang HC, Chuang HC, Hsu YC, Yang MY and Chien CY: Pre-treatment with angiotensin-(1–7) inhibits tumor growth via autophagy by downregulating PI3K/Akt/mTOR signaling in human nasopharyngeal carcinoma xenografts. J Mol Med (Berl). 96:1407–1418. 2018. View Article : Google Scholar : PubMed/NCBI

111 

Pei N, Wan R, Chen X, Li A, Zhang Y, Li J, Du H, Chen B, Wei W, Qi Y, et al: Angiotensin-(1–7) decreases cell growth and angiogenesis of human nasopharyngeal carcinoma xenografts. Mol Cancer Ther. 15:37–47. 2016. View Article : Google Scholar : PubMed/NCBI

112 

Fountzilas E, Kotoula V, Angouridakis N, Karasmanis I, Wirtz RM, Eleftheraki AG, Veltrup E, Markou K, Nikolaou A, Pectasides D and Fountzilas G: Identification and validation of a multigene predictor of recurrence in primary laryngeal cancer. PLoS One. 8:e704292013. View Article : Google Scholar : PubMed/NCBI

113 

Zhao Y, Zhao Z, Wang Y, Zhou Y, Ma Y and Zuo W: Single-cell RNA expression profiling of ACE2, the receptor of SARS-CoV-2. Am J Respir Crit Care Med. 202:756–759. 2020. View Article : Google Scholar : PubMed/NCBI

114 

Ciechanowicz AK, Lay WX, Prado Paulino J, Suchocki E, Leszczak S, Leszczak C and Kucia M: Angiotensin 1–7 stimulates proliferation of lung bronchoalveolar progenitors-implications for SARS-CoV-2 infection. Cells. 11:21022022. View Article : Google Scholar : PubMed/NCBI

115 

Salahudeen AA, Choi SS, Rustagi A, Zhu J, van Unen V, de la O SM, Flynn RA, Margalef-Català M, Santos AJM, Ju J, et al: Progenitor identification and SARS-CoV-2 infection in human distal lung organoids. Nature. 588:670–675. 2020. View Article : Google Scholar : PubMed/NCBI

116 

Sidarta-Oliveira D, Jara CP, Ferruzzi AJ, Skaf MS, Velander WH, Araujo EP and Velloso LA: SARS-CoV-2 receptor is co-expressed with elements of the kinin-kallikrein, renin-angiotensin and coagulation systems in alveolar cells. Sci Rep. 10:195222020. View Article : Google Scholar : PubMed/NCBI

117 

Qiao Y, Wang XM, Mannan R, Pitchiaya S, Zhang Y, Wotring JW, Xiao L, Robinson DR, Wu YM, Tien JC, et al: Targeting transcriptional regulation of SARS-CoV-2 entry factors ACE2 and TMPRSS2. Proc Natl Acad Sci USA. 118:e20214501182020. View Article : Google Scholar : PubMed/NCBI

118 

Liu A, Zhang X, Li R, Zheng M, Yang S, Dai L, Wu A, Hu C, Huang Y, Xie M and Chen Q: Overexpression of the SARS-CoV-2 receptor ACE2 is induced by cigarette smoke in bronchial and alveolar epithelia. J Pathol. 253:17–30. 2021. View Article : Google Scholar : PubMed/NCBI

119 

Cai G: Bulk and single-cell transcriptomics identify tobacco-use disparity in lung gene expression of ACE2. medRxiv. Feb 28–2020.doi: 10.1101/2020.02.05.20020107.

120 

Cai G, Bosse Y, Xiao F, Kheradmand F and Amos CI: Tobacco smoking increases the lung gene expression of ACE2, the receptor of SARS-CoV-2. Am J Respir Crit Care Med. 201:1557–1559. 2020. View Article : Google Scholar : PubMed/NCBI

121 

Lukassen S, Chua RL, Trefzer T, Kahn NC, Schneider MA, Muley T, Winter H, Meister M, Veith C, Boots AW, et al: SARS-CoV-2 receptor ACE2 and TMPRSS2 are primarily expressed in bronchial transient secretory cells. EMBO J. 39:e1051142020. View Article : Google Scholar : PubMed/NCBI

122 

Voinsky I and Gurwitz D: Smoking and COVID-19: Similar bronchial ACE2 and TMPRSS2 expression and higher TMPRSS4 expression in current versus never smokers. Drug Dev Res. 81:1073–1080. 2020. View Article : Google Scholar : PubMed/NCBI

123 

Chen F, Matsuda A, Budinger GRS, Sporn PHS and Casalino-Matsuda SM: Hypercapnia increases ACE2 expression and pseudo–SARS–CoV–2 entry in bronchial epithelial cells by augmenting cellular cholesterol. Front Immunol. 14:12511202023. View Article : Google Scholar : PubMed/NCBI

124 

Ilikci Sagkan R and Akin-Bali DF: Structural variations and expression profiles of the SARS-CoV-2 host invasion genes in lung cancer. J Med Virol. 92:2637–2647. 2020. View Article : Google Scholar : PubMed/NCBI

125 

Zhang H, Quek K, Chen R, Chen J and Chen B: Expression of the SAR2-Cov-2 receptor ACE2 reveals the susceptibility of COVID-19 in non-small cell lung cancer. J Cancer. 11:5289–5292. 2020. View Article : Google Scholar : PubMed/NCBI

126 

Subbarayan K, Ulagappan K, Wickenhauser C and Seliger B: xpression and Clinical Significance of SARS-CoV-2 human targets in neoplastic and non-neoplastic lung tissues. Curr Cancer Drug Targets. 21:428–442. 2021. View Article : Google Scholar : PubMed/NCBI

127 

Wang Q, Li L, Qu T, Li J, Wu L, Li K, Wang Z, Zhu M, Huang B, Wu W, et al: High expression of ACE2 and TMPRSS2 at the resection margin makes lung cancer survivors susceptible to SARS-CoV-2 with unfavorable prognosis. Front Oncol. 11:6445752021. View Article : Google Scholar : PubMed/NCBI

128 

Liu Z, Gu X, Li Z, Shan S, Wu F and Ren T: Heterogeneous expression of ACE2, TMPRSS2, and FURIN at single-cell resolution in advanced non-small cell lung cancer. J Cancer Res Clin Oncol. 149:3563–3573. 2023. View Article : Google Scholar : PubMed/NCBI

129 

Hoang T, Nguyen TQ and Tran TTA: Genetic susceptibility of ACE2 and TMPRSS2 in six common cancers and possible impacts on COVID-19. Cancer Res Treat. 53:650–656. 2021. View Article : Google Scholar : PubMed/NCBI

130 

Kong Q, Xiang Z, Wu Y, Gu Y, Guo J and Geng F: Analysis of the susceptibility of lung cancer patients to SARS-CoV-2 infection. Mol Cancer. 19:802020. View Article : Google Scholar : PubMed/NCBI

131 

He C, Hua X, Sun S, Li S, Wang J and Huang X: Integrated bioinformatic analysis of SARS-CoV-2 infection related genes ACE2, BSG and TMPRSS2 in aerodigestive cancers. J Inflamm Res. 14:791–802. 2021. View Article : Google Scholar : PubMed/NCBI

132 

Hayashi T, Sano K and Konishi I: Possibility of SARS-CoV-2 infection in the metastatic microenvironment of cancer. Curr Issues Mol Biol. 44:233–241. 2022. View Article : Google Scholar : PubMed/NCBI

133 

Samad A, Jafar T and Rafi JH: Identification of angiotensin-converting enzyme 2 (ACE2) protein as the potential biomarker in SARS-CoV-2 infection-related lung cancer using computational analyses. Genomics. 112:4912–4923. 2020. View Article : Google Scholar : PubMed/NCBI

134 

Lazar V, Raynaud J, Magidi S, Bresson C, Martini JF, Galbraith S, Wunder F, Onn A, Batist G, Girard N, et al: Comorbidity between lung cancer and COVID-19 pneumonia: Role of immunoregulatory gene transcripts in high ACE2-expressing normal lung. Ther Adv Med Oncol. 14:175883592211338932022. View Article : Google Scholar : PubMed/NCBI

135 

Dai YJ, Hu F, Li H, Huang HY, Wang DW and Liang Y: A profiling analysis on the receptor ACE2 expression reveals the potential risk of different type of cancers vulnerable to SARS-CoV-2 infection. Ann Transl Med. 8:4812020. View Article : Google Scholar : PubMed/NCBI

136 

Deben C, Le Compte M, Siozopoulou V, Lambrechts H, Hermans C, Lau HW, Huizing M, Lamote K, Hendriks JMH, Van Dam P, et al: Expression of SARS-CoV-2-Related surface proteins in non-small-cell lung cancer patients and the influence of standard of care therapy. Cancers (Basel). 14:40742022. View Article : Google Scholar : PubMed/NCBI

137 

Yamaguchi M, Hirai S, Sumi T, Tanaka Y, Tada M, Nishii Y, Hasegawa T, Uchida H, Yamada G, Watanabe A, et al: Angiotensin-converting enzyme 2 is a potential therapeutic target for EGFR-mutant lung adenocarcinoma. Biochem Biophys Res Commun. 487:613–618. 2017. View Article : Google Scholar : PubMed/NCBI

138 

Feng Y, Wan H, Liu J, Zhang R, Ma Q, Han B, Xiang Y, Che J, Cao H, Fei X and Qiu W: The angiotensin-converting enzyme 2 in tumor growth and tumor-associated angiogenesis in non-small cell lung cancer. Oncol Rep. 23:941–948. 2010.PubMed/NCBI

139 

Teng JP, Yang ZY, Zhu YM, Ni D, Zhu ZJ and Li XQ: Gemcitabine and cisplatin for treatment of lung cancer in vitro and vivo. Eur Rev Med Pharmacol Sci. 22:3819–3825. 2018.PubMed/NCBI

140 

Cheng Q, Zhou L, Zhou J, Wan H, Li Q and Feng Y: ACE2 overexpression inhibits acquired platinum resistance-induced tumor angiogenesis in NSCLC. Oncol Rep. 36:1403–1410. 2016. View Article : Google Scholar : PubMed/NCBI

141 

Feng Y, Ni L, Wan H, Fan L, Fei X, Ma Q, Gao B, Xiang Y, Che J and Li Q: Overexpression of ACE2 produces antitumor effects via inhibition of angiogenesis and tumor cell invasion in vivo and in vitro. Oncol Rep. 26:1157–1164. 2011.PubMed/NCBI

142 

Qian YR, Guo Y, Wan HY, Fan L, Feng Y, Ni L, Xiang Y and Li QY: Angiotensin-converting enzyme 2 attenuates the metastasis of non-small cell lung cancer through inhibition of epithelial-mesenchymal transition. Oncol Rep. 29:2408–2414. 2013. View Article : Google Scholar : PubMed/NCBI

143 

Wilop S, von Hobe S, Crysandt M, Esser A, Osieka R and Jost E: Impact of angiotensin I converting enzyme inhibitors and angiotensin II type 1 receptor blockers on survival in patients with advanced non-small-cell lung cancer undergoing first-line platinum-based chemotherapy. J Cancer Res Clin Oncol. 135:1429–1435. 2009. View Article : Google Scholar : PubMed/NCBI

144 

Menon J, Soto-Pantoja DR, Callahan MF, Cline JM, Ferrario CM, Tallant EA and Gallagher PE: Angiotensin-(1–7) inhibits growth of human lung adenocarcinoma xenografts in nude mice through a reduction in cyclooxygenase-2. Cancer Res. 67:2809–2815. 2007. View Article : Google Scholar : PubMed/NCBI

145 

Hicks BM, Filion KB, Yin H, Sakr L, Udell JA and Azoulay L: Angiotensin converting enzyme inhibitors and risk of lung cancer: Population based cohort study. BMJ. 363:k42092018. View Article : Google Scholar : PubMed/NCBI

146 

Sheinin M, Jeong B, Paidi RK and Pahan K: Regression of lung cancer in mice by intranasal administration of SARS-CoV-2 spike S1. Cancers (Basel). 14:56482022. View Article : Google Scholar : PubMed/NCBI

147 

Li X, Zhou C and Hu W: Association between serum angiotensin-converting enzyme 2 level with postoperative morbidity and mortality after major pulmonary resection in non-small cell lung cancer patients. Heart Lung Circ. 23:661–666. 2014. View Article : Google Scholar : PubMed/NCBI

148 

Jiang Y, Chen L, Shen J, Mei X, Yao J, Chen T and Zhou Y: The potential role of abnormal angiotensin-converting enzyme 2 expression correlated with immune infiltration after SARS-CoV-2 infection in the prognosis of breast cancer. Aging. 13:20886–20895. 2021. View Article : Google Scholar : PubMed/NCBI

149 

Mei J, Cai Y, Xu R, Yu X, Han X, Weng M, Chen L, Ma T, Gao T, Gao F, et al: Angiotensin-converting enzyme 2 identifies immune-hot tumors suggesting angiotensin-(1–7) as a sensitizer for chemotherapy and immunotherapy in breast cancer. Biol Proced Online. 24:152022. View Article : Google Scholar : PubMed/NCBI

150 

Zuo X, Ren S, Zhang H, Tian J, Tian R, Han B, Liu H, Dong Q, Wang Z, Cui Y, et al: Chemotherapy induces ACE2 expression in breast cancer via the ROS-AKT-HIF-1α signaling pathway: A potential prognostic marker for breast cancer patients receiving chemotherapy. J Transl Med. 20:5092022. View Article : Google Scholar : PubMed/NCBI

151 

Ling J, Peng N and Luo L: ACE2 maybe serve as a prognostic biomarker in breast invasive carcinoma. J Clin Lab Anal. 36:e243622022. View Article : Google Scholar : PubMed/NCBI

152 

Zhang Q, Lu S, Li T, Yu L, Zhang Y, Zeng H, Qian X, Bi J and Lin Y: ACE2 inhibits breast cancer angiogenesis via suppressing the VEGFa/VEGFR2/ERK pathway. J Exp Clin Cancer Res. 38:1732019. View Article : Google Scholar : PubMed/NCBI

153 

Yu C, Tang W, Wang Y, Shen Q, Wang B, Cai C, Meng X and Zou F: Downregulation of ACE2/Ang-(1–7)/Mas axis promotes breast cancer metastasis by enhancing store-operated calcium entry. Cancer Lett. 376:268–277. 2016. View Article : Google Scholar : PubMed/NCBI

154 

Nair MG, Prabhu JS and Ts S: High expression of ACE2 in HER2 subtype of breast cancer is a marker of poor prognosis. Cancer Treat Res Commun. 27:1003212021. View Article : Google Scholar : PubMed/NCBI

155 

Nowak JK, Lindstrøm JC, Kalla R, Ricanek P, Halfvarson J and Satsangi J: Age, inflammation, and disease location are critical determinants of intestinal expression of SARS-CoV-2 receptor ACE2 and TMPRSS2 in inflammatory bowel disease. Gastroenterology. 159:1151–1154. 2020. View Article : Google Scholar : PubMed/NCBI

156 

Verstockt B, Verstockt S, Abdu Rahiman S, Ke BJ, Arnauts K, Cleynen I, Sabino J, Ferrante M, Matteoli G and Vermeire S: Intestinal receptor of SARS-CoV-2 in Inflamed IBD tissue seems downregulated by HNF4A in ileum and upregulated by interferon regulating factors in colon. J Crohns Colitis. 15:485–498. 2021. View Article : Google Scholar : PubMed/NCBI

157 

Brandão TB, Gueiros LA, Melo TS, Prado-Ribeiro AC, Nesrallah ACFA, Prado GVB, Santos-Silva AR and Migliorati CA: Oral lesions in patients with SARS-CoV-2 infection: Could the oral cavity be a target organ? Oral Surg Oral Med Oral Pathol Oral Radiol. 31:45–51. 2021. View Article : Google Scholar

158 

Xu J, Chu M, Zhong F, Tan X, Tang G, Mai J, Lai N, Guan C, Liang Y and Liao G: Digestive symptoms of COVID-19 and expression of ACE2 in digestive tract organs. Cell Death Discov. 6:762020. View Article : Google Scholar : PubMed/NCBI

159 

Desquilles L, Cano L, Ghukasyan G, Mouchet N, Landreau C, Corlu A, Clément B, Turlin B, Désert R and Musso O: Well-differentiated liver cancers reveal the potential link between ACE2 dysfunction and metabolic breakdown. Sci Rep. 12:18592022. View Article : Google Scholar : PubMed/NCBI

160 

Stevens JP, Kolachala VL, Joshi GN, Nagpal S, Gibson G and Gupta NA: Angiotensin-converting enzyme-2 (ACE2) expression in pediatric liver disease. Appl Immunohistochem Mol Morphol. 30:647–653. 2022. View Article : Google Scholar : PubMed/NCBI

161 

Osterreicher CH, Taura K, De Minicis S, Seki E, Penz-Osterreicher M, Kodama Y, Kluwe J, Schuster M, Oudit GY, Penninger JM and Brenner DA: Angiotensin-converting-enzyme 2 inhibits liver fibrosis in mice. Hepatology. 50:929–938. 2009. View Article : Google Scholar : PubMed/NCBI

162 

Dong F, Li H, Liu L, Yao LL, Wang J, Xiang D, Ma J, Zhang G, Zhang S, Li J, et al: ACE2 negatively regulates the Warburg effect and suppresses hepatocellular carcinoma progression via reducing ROS-HIF1α activity. Int J Biol Sci. 19:2613–2629. 2023. View Article : Google Scholar : PubMed/NCBI

163 

Paizis G, Tikellis C, Cooper ME, Schembri JM, Lew RA, Smith AI, Shaw T, Warner FJ, Zuilli A, Burrell LM and Angus PW: Chronic liver injury in rats and humans upregulates the novel enzyme angiotensin converting enzyme 2. Gut. 54:1790–1796. 2005. View Article : Google Scholar : PubMed/NCBI

164 

Herath CB, Warner FJ, Lubel JS, Dean RG, Jia Z, Lew RA, Smith AI, Burrell LM and Angus PW: Upregulation of hepatic angiotensin-converting enzyme 2 (ACE2) and angiotensin-(1–7) levels in experimental biliary fibrosis. J Hepatol. 47:387–395. 2007. View Article : Google Scholar : PubMed/NCBI

165 

Ye G, Qin Y, Lu X, Xu X, Xu S, Wu C, Wang X, Wang S and Pan D: The association of renin-angiotensin system genes with the progression of hepatocellular carcinoma. Biochem Biophys Res Commun. 459:18–23. 2015. View Article : Google Scholar : PubMed/NCBI

166 

Domovitz T, Ayoub S, Werbner M, Alter J, Izhaki Tavor L, Yahalom-Ronen Y, Tikhonov E, Meirson T, Maman Y, Paran N, et al: HCV infection increases the expression of ACE2 receptor, leading to enhanced entry of both HCV and SARS-CoV-2 into hepatocytes and a coinfection state. Microbiol Spectr. 10:e01150222022. View Article : Google Scholar : PubMed/NCBI

167 

Li J, Yang ZL, Ren X, Zou Q, Yuan Y, Liang L, Chen M and Chen S: ACE2 and FZD1 are prognosis markers in squamous cell/adenosquamous carcinoma and adenocarcinoma of gallbladder. J Mol Histol. 45:47–57. 2014. View Article : Google Scholar : PubMed/NCBI

168 

Zong H, Yin B, Zhou H, Cai D, Ma B and Xiang Y: Loss of angiotensin-converting enzyme 2 promotes growth of gallbladder cancer. Tumour Biol. 36:5171–5177. 2015. View Article : Google Scholar : PubMed/NCBI

169 

Lee JJ, Kopetz S, Vilar E, Shen JP, Chen K and Maitra A: Relative abundance of SARS-CoV-2 Entry genes in the enterocytes of the lower gastrointestinal tract. Genes (Basel). 11:6452020. View Article : Google Scholar : PubMed/NCBI

170 

Suárez-Fariñas M, Tokuyama M, Wei G, Huang R, Livanos A, Jha D, Levescot A, Irizar H, Kosoy R, Cording S, et al: Intestinal inflammation modulates the expression of ACE2 and TMPRSS2 and potentially overlaps with the pathogenesis of SARS-CoV-2-related disease. Gastroenterology. 160:287–301.e20. 2021. View Article : Google Scholar : PubMed/NCBI

171 

Hashimoto T, Perlot T, Rehman A, Trichereau J, Ishiguro H, Paolino M, Sigl V, Hanada T, Hanada R, Lipinski S, et al: ACE2 links amino acid malnutrition to microbial ecology and intestinal inflammation. Nature. 487:477–481. 2012. View Article : Google Scholar : PubMed/NCBI

172 

Bao R, Hernandez K, Huang L and Luke JJ: ACE2 and TMPRSS2 expression by clinical, HLA, immune, and microbial correlates across 34 human cancers and matched normal tissues: Implications for SARS-CoV-2 COVID-19. J Immunother Cancer. 8:e0010202020. View Article : Google Scholar : PubMed/NCBI

173 

Duan Y, Prasad R, Feng D, Beli E, Li Calzi S, Longhini ALF, Lamendella R, Floyd JL, Dupont M, Noothi SK, et al: Bone Marrow-derived cells restore functional integrity of the gut epithelial and vascular barriers in a model of diabetes and ACE2 deficiency. Circ Res. 125:969–988. 2019. View Article : Google Scholar : PubMed/NCBI

174 

Nataf S and Pays L: Molecular Insights into SARS-CoV2-induced alterations of the Gut/Brain axis. Int J Mol Sci. 22:104402021. View Article : Google Scholar : PubMed/NCBI

175 

Liu C, Xiao L, Li F, Zhang H, Li Q, Liu H, Fu S, Li C, Zhang X, Wang J, et al: Generation of outbred Ace2 knockout mice by RNA transfection of TALENs displaying colitis reminiscent pathophysiology and inflammation. Transgenic Res. 24:433–46. 2015. View Article : Google Scholar : PubMed/NCBI

176 

Shahrokh S, Baradaran Ghavami S, Asadzadeh Aghdaei H, Parigi TL, Farmani M, Danese S, Ebrahimi Daryani N, Vossoughinia H, Balaii H, Alborzi F, et al: High prevalence of SARS-Coronavirus-2 in patients with inflammatory bowel disease and the role of soluble angiotensin converting enzyme 2. Arch Physiol Biochem. 130:325–332. 2024. View Article : Google Scholar : PubMed/NCBI

177 

Potdar AA, Dube S, Naito T, Li K, Botwin G, Haritunians T, Li D, Casero D, Yang S, Bilsborough J, et al: Altered intestinal ACE2 levels are associated with inflammation, severe disease, and response to Anti-cytokine therapy in inflammatory bowel disease. Gastroenterology. 160:809–822. 2021. View Article : Google Scholar : PubMed/NCBI

178 

Yang K and Wang Y: Dandelion root extracts and taraxasterol inhibit LPS-induced colorectal cancer cell viability by blocking TLR4-NFκB-driven ACE2 and TMPRSS2 pathways. Exp Ther Med. 27:2562024. View Article : Google Scholar : PubMed/NCBI

179 

Wang H and Yang J: Colorectal cancer that highly express both ACE2 and TMPRSS2, suggesting severe symptoms to SARS-CoV-2 infection. Pathol Oncol Res. 27:6129692021. View Article : Google Scholar : PubMed/NCBI

180 

Liu C, Wang K, Zhang M, Hu X, Hu T, Liu Y, Hu Q, Wu S and Yue J: High expression of ACE2 and TMPRSS2 and clinical characteristics of COVID-19 in colorectal cancer patients. NPJ Precis Oncol. 5:12021. View Article : Google Scholar : PubMed/NCBI

181 

Chen Y, Gong W, Wei H, Dai W and Xu S: 2019-nCoV may create complications in colon cancer patients with ACE2 expression. Int J Clin Exp Pathol. 13:2305–2311. 2020.PubMed/NCBI

182 

Li S, Chen S, Zhu Q, Ben S, Gao F, Xin J, Du M, Chu H, Gu D, Zhang Z and Wang M: The impact of ACE2 and co-factors on SARS-CoV-2 infection in colorectal cancer. Clin Transl Med. 12:e9672022. View Article : Google Scholar : PubMed/NCBI

183 

Chen H, Zou TH, Xuan B, Yan Y, Yan T, Shen C, Zhao G, Chen YX, Xiao X, Hong J and Fang JY: Single cell transcriptome revealed SARS-CoV-2 entry genes enriched in colon tissues and associated with coronavirus infection and cytokine production. Signal Transduct Target Ther. 5:1212020. View Article : Google Scholar : PubMed/NCBI

184 

Ahmadi M, Pashangzadeh S, Mousavi P, Saffarzadeh N, Amin Habibi M, Hajiesmaeili F and Rezaei N: ACE2 correlates with immune infiltrates in colon adenocarcinoma: Implication for COVID-19. Int Immunopharmacol. 95:1075682021. View Article : Google Scholar : PubMed/NCBI

185 

Zhang S, Kapoor S, Tripathi C, Perez JT, Mohan N, Dashwood WM, Zhang K, Rajendran P and Dashwood R: Targeting ACE2-BRD4 crosstalk in colorectal cancer and the deregulation of DNA repair and apoptosis. NPJ Precis Oncol. 7:202023. View Article : Google Scholar : PubMed/NCBI

186 

Triana S, Metz-Zumaran C, Ramirez C, Kee C, Doldan P, Shahraz M, Schraivogel D, Gschwind AR, Sharma AK, Steinmetz LM, et al: Single-cell analyses reveal SARS-CoV-2 interference with intrinsic immune response in the human gut. Mol Syst Biol. 17:e102322021. View Article : Google Scholar : PubMed/NCBI

187 

Lamers MM, Beumer J, van der Vaart J, Knoops K, Puschhof J, Breugem TI, Ravelli RBG, Paul van Schayck J, Mykytyn AZ, Duimel HQ, et al: SARS-CoV-2 productively infects human gut enterocytes. Science. 369:50–54. 2020. View Article : Google Scholar : PubMed/NCBI

188 

Ottaiano A, Scala S, D'Alterio C, D'Alterio C, Trotta A, Bello A, Rea G, Picone C, Santorsola M, Petrillo A and Nasti G: Unexpected tumor reduction in metastatic colorectal cancer patients during SARS-Cov-2 infection. Ther J Med Oncol. 13:175883592110114552021. View Article : Google Scholar : PubMed/NCBI

189 

Cappello F, Burgio S, Conway de Macario E and Macario AJL: Unexpected tumor reduction in metastatic colorectal cancer patients during SARS-Cov-2 infection: Effect of ACE-2 expression on tumor cells or molecular mimicry phenomena? Two not mutually exclusive hypotheses. Ther Adv Med Oncol. 13:175883592110278252021. View Article : Google Scholar : PubMed/NCBI

190 

Pakbin B, Dibazar SP, Allahyari S, Shariatifar H, Brück WM and Farasat A: ACE2-inhibitory effects of bromelain and ficin in colon cancer cells. Medicina (Kaunas). 59:3012023. View Article : Google Scholar : PubMed/NCBI

191 

Li N, Zimpelmann J, Cheng K, Wilkins JA and Burns KD: The role of angiotensin converting enzyme 2 in the generation of angiotensin 1–7 by rat proximal tubules. Am J Physiol Renal Physiol. 288:F353–F362. 2005. View Article : Google Scholar : PubMed/NCBI

192 

Fan C, Lu W, Li K, Ding Y and Wang J: ACE2 expression in kidney and testis may cause kidney and testis infection in COVID-19 patients. Front Med (Lausanne). 13:5638932021. View Article : Google Scholar

193 

He Q, Mok TN, Yun L, He C, Li J and Pan J: Single-cell RNA sequencing analysis of human kidney reveals the presence of ACE2 receptor: A potential pathway of COVID-19 infection. Mol Genet Genomic Med. 8:e14422020. View Article : Google Scholar : PubMed/NCBI

194 

Lin W, Fan J, Hu LF, Zhang Y, Ooi JD, Meng T, Jin P, Ding X, Peng LK, Song L, et al: Single-cell analysis of angiotensin-converting enzyme II expression in human kidneys and bladders reveals a potential route of 2019 novel coronavirus infection. Chin Med J (Engl). 134:935–943. 2021. View Article : Google Scholar : PubMed/NCBI

195 

Pan XW, Xu D, Zhang H, Zhou W, Wang LH and Cui XG: Identification of a potential mechanism of acute kidney injury during the COVID-19 outbreak: A study based on single-cell transcriptome analysis. Intensive Care Med. 46:1114–1116. 2020. View Article : Google Scholar : PubMed/NCBI

196 

Tikellis C, Johnston CI, Forbes JM, Burns WC, Burrell LM, Risvanis J and Cooper ME: Characterization of renal angiotensin-converting enzyme 2 in diabetic nephropathy. Hypertension. 41:392–397. 2003. View Article : Google Scholar : PubMed/NCBI

197 

Soler MJ, Wysocki J, Ye M, Lloveras J, Kanwar Y and Batlle D: ACE2 inhibition worsens glomerular injury in association with increased ACE expression in streptozotocin-induced diabetic mice. Kidney Int. 72:614–623. 2007. View Article : Google Scholar : PubMed/NCBI

198 

Vergara A, Wang K, Colombo D, Gheblawi M, Rasmuson J, Mandal R, Del Nonno F, Chiu B, Scholey JW, Soler MJ, et al: Urinary angiotensin-converting enzyme 2 and metabolomics in COVID-19-mediated kidney injury. Clin Kidney J. 16:272–284. 2022. View Article : Google Scholar : PubMed/NCBI

199 

Burns WC, Velkoska E, Dean R, Burrell LM and Thomas MC: Angiotensin II mediates epithelial-to-mesenchymal transformation in tubular cells by ANG 1–7/MAS-1-dependent pathways. Am J Physiol Renal Physiol. 299:F585–F593. 2010. View Article : Google Scholar : PubMed/NCBI

200 

Choong OK, Jakobsson R, Bergdahl AG, Brunet S, Kärmander A, Waldenström J, Arvidsson Y, Altiparmak G, Nilsson JA, Karlsson J, et al: SARS-CoV-2 replicates and displays oncolytic properties in clear cell and papillary renal cell carcinoma. PLoS One. 18:e02795782023. View Article : Google Scholar : PubMed/NCBI

201 

Larrinaga G, Pérez I, Sanz B, Blanco L, López JI, Cándenas ML, Pinto FM, Gil J, Irazusta J and Varona A: Angiotensin-converting enzymes (ACE and ACE2) are downregulated in renal tumors. Regul Pept. 165:218–23. 2010. View Article : Google Scholar : PubMed/NCBI

202 

Errarte P, Beitia M, Perez I, Manterola L, Lawrie CH, Solano-Iturri JD, Calvete-Candenas J, Unda M, López JI and Larrinaga G: Expression and activity of angiotensin-regulating enzymes is associated with prognostic outcome in clear cell renal cell carcinoma patients. PLoS One. 12:e01817112017. View Article : Google Scholar : PubMed/NCBI

203 

Niu X, Zhu Z, Shao E and Bao J: ACE2 is a prognostic biomarker and associated with immune infiltration in kidney renal clear cell carcinoma: Implication for COVID-19. J Oncol. 2021:88473072021. View Article : Google Scholar : PubMed/NCBI

204 

Yang W, Li L, Zhang K, Ma K, Xie H, Gong Y, Zhou J and Gong K: ACE2 correlated with immune infiltration serves as a novel prognostic biomarker in clear cell renal cell carcinoma: Implication for COVID-19. Int J Biol Sci. 17:20–31. 2021. View Article : Google Scholar : PubMed/NCBI

205 

Yang J, Li H, Hu S and Zhou Y: ACE2 correlated with immune infiltration serves as a prognostic biomarker in endometrial carcinoma and renal papillary cell carcinoma: Implication for COVID-19. Aging (Albany NY). 12:6518–6535. 2020. View Article : Google Scholar : PubMed/NCBI

206 

Tang Q, Wang Y, Ou L, Li J, Zheng K, Zhan H, Gu J, Zhou G, Xie S, Zhang J, et al: Downregulation of ACE2 expression by SARS-CoV-2 worsens the prognosis of KIRC and KIRP patients via metabolism and immunoregulation. Int J Biol Sci. 17:1925–1939. 2021. View Article : Google Scholar : PubMed/NCBI

207 

Siljee S, Milne B, Brasch HD, Bockett N, Patel J, Davis PF, Kennedy-Smith A, Itinteang T and Tan ST: Expression of components of the Renin-angiotensin system by cancer stem cells in renal clear cell carcinoma. Biomolecules. 11:5372021. View Article : Google Scholar : PubMed/NCBI

208 

Cane R, Kennedy-Smith A, Brasch HD, Savage S, Marsh RW and Itinteang T, Tan ST and Itinteang T: Characterization of cancer stem cells in renal clear cell carcinoma. J Stem Cell Regen Biol. 5:6–17. 2019.

209 

Wang T, Xie F, Li YH and Liang B: Downregulation of ACE2 is associated with advanced pathological features and poor prognosis in clear cell renal cell carcinoma. Future Oncol. 17:5033–5044. 2021. View Article : Google Scholar : PubMed/NCBI

210 

Khanna P, Soh HJ, Chen CH, Saxena R, Amin S, Naughton M, Joslin PN, Moore A, Bakouny Z, O'Callaghan C, et al: ACE2 abrogates tumor resistance to VEGFR inhibitors suggesting angiotensin-(1–7) as a therapy for clear cell renal cell carcinoma. Sci Transl Med. 13:eabc01702021. View Article : Google Scholar : PubMed/NCBI

211 

Li Q, Yang W, Lu M and Zhang R: Identification of a 6-Gene signature associated with resistance to tyrosine kinase inhibitors: Prognosis for clear cell renal cell carcinoma. Med Sci Monit. 26:e9270782020. View Article : Google Scholar : PubMed/NCBI

212 

Douglas GC, O'Bryan MK, Hedger MP, Lee DK, Yarski MA, Smith AI and Lew RA: The novel angiotensin-converting enzyme (ACE) homolog, ACE2, is selectively expressed by adult Leydig cells of the testis. Endocrinology. 145:4703–4711. 2004. View Article : Google Scholar : PubMed/NCBI

213 

Wang Z and Xu X: scRNA-seq profiling of human testes reveals the presence of the ACE2 receptor, a target for SARS-CoV-2 infection in spermatogonia, leydig and sertoli cells. Cells. 9:9202020. View Article : Google Scholar : PubMed/NCBI

214 

Ribeiro MR, Calado AM, Alves Â, Pereira R, Sousa M and Sá R: Spatial distribution of SARS-CoV-2 receptors and proteases in testicular cells. J Histochem Cytochem. 71:169–197. 2023. View Article : Google Scholar : PubMed/NCBI

215 

Liu X, Chen Y, Tang W, Zhang L, Chen W, Yan Z, Yuan P, Yang M, Kong S, Yan L and Qiao J: Single-cell transcriptome analysis of the novel coronavirus (SARS-CoV-2) associated gene ACE2 expression in normal and non-obstructive azoospermia (NOA) human male testes. Sci China Life Sci. 63:1006–1015. 2020. View Article : Google Scholar : PubMed/NCBI

216 

Shen Q, Xiao X, Aierken A, Yue W, Wu X, Liao M and Hua J: The ACE2 expression in Sertoli cells and germ cells may cause male reproductive disorder after SARS-CoV-2 infection. J Cell Mol Med. 24:9472–9477. 2020. View Article : Google Scholar : PubMed/NCBI

217 

Gianzo M and Subirán N: Regulation of male fertility by the Renin-angiotensin system. Int J Mol Sci. 21:79432020. View Article : Google Scholar : PubMed/NCBI

218 

Reis AB, Araújo FC, Pereira VM, Dos Reis AM, Santos RA and Reis FM: Angiotensin (1–7) and its receptor Mas are expressed in the human testis: Implications for male infertility. J Mol Histol. 41:75–80. 2010. View Article : Google Scholar : PubMed/NCBI

219 

Song H, Seddighzadeh B, Cooperberg MR and Huang FW: Expression of ACE2, the SARS-CoV-2 Receptor, and TMPRSS2 in prostate epithelial cells. Eur Urol. 78:296–298. 2020. View Article : Google Scholar : PubMed/NCBI

220 

Krishnan B, Smith TL, Dubey P, Zapadka ME, Torti FM, Willingham MC, Tallant EA and Gallagher PE: Angiotensin-(1–7) attenuates metastatic prostate cancer and reduces osteoclastogenesis. Prostate. 73:71–82. 2013. View Article : Google Scholar : PubMed/NCBI

221 

Krishnan B, Torti FM, Gallagher PE and Tallant EA: Angiotensin-(1–7) reduces proliferation and angiogenesis of human prostate cancer xenografts with a decrease in angiogenic factors and an increase in sFlt-1. Prostate. 73:60–70. 2013. View Article : Google Scholar : PubMed/NCBI

222 

Bhowmick NA, Oft J, Dorff T, Pal S, Agarwal N, Figlin RA, Posadas EM, Freedland SJ and Gong J: COVID-19 and androgen-targeted therapy for prostate cancer patients. Endocr Relat Cancer. 27:R281–R292. 2020. View Article : Google Scholar : PubMed/NCBI

223 

Vaz-Silva J, Carneiro MM, Ferreira MC, Pinheiro SV, Silva DA, Silva-Filho AL, Witz CA, Reis AM, Santos RA and Reis FM: The vasoactive peptide angiotensin-(1–7), its receptor Mas and the angiotensin-converting enzyme type 2 are expressed in the human endometrium. Reprod Sci. 16:247–256. 2009. View Article : Google Scholar : PubMed/NCBI

224 

Chadchan SB, Popli P, Maurya VK and Kommagani R: The SARS-CoV-2 receptor, angiotensin-converting enzyme 2, is required for human endometrial stromal cell decidualization. Biol Reprod. 104:336–343. 2021. View Article : Google Scholar : PubMed/NCBI

225 

Qin S, Zhou YJ, Liu Y, Shen HM, Li XD, Yan X and Tang HJ: Expression and significance of ACE2-Ang-(1–7)-Mas axis in the endometrium of patients with polycystic ovary syndrome. Zhonghua Yi Xue Za Zhi. 93:1989–1992. 2013.(In Chinese). PubMed/NCBI

226 

Haouzi D, Entezami F, Tuaillon E, Gala A, Ferrières-Hoa A, Brouillet S, Thierry AR and Hamamah S: SARS-CoV-2 and implantation window: Gene expression mapping of human endometrium and preimplantation embryo. Life (Basel). 11:13782021.PubMed/NCBI

227 

Naigaonkar A, Patil K, Joseph S, Hinduja I and Mukherjee S: Ovarian granulosa cells from women with PCOS express low levels of SARS-CoV-2 receptors and co-factors. Arch Gynecol Obstet. 306:547–555. 2022. View Article : Google Scholar : PubMed/NCBI

228 

Guo X, Semerci N, De Assis V, Kayisli UA, Schatz F, Steffensen TS, Guzeloglu-Kayisli O and Lockwood CJ: Regulation of proinflammatory molecules and tissue factor by SARS-CoV-2 spike protein in human placental cells: Implications for SARS-CoV-2 pathogenesis in pregnant women. Front Immunol. 13:8765552022. View Article : Google Scholar : PubMed/NCBI

229 

Valdés G, Neves LA, Anton L, Corthorn J, Chacón C, Germain AM, Merrill DC, Ferrario CM, Sarao R, Penninger J and Brosnihan KB: Distribution of angiotensin-(1–7) and ACE2 in human placentas of normal and pathological pregnancies. Placenta. 27:200–207. 2006. View Article : Google Scholar : PubMed/NCBI

230 

Essahib W, Verheyen G, Tournaye H and Van de Velde H: SARS-CoV-2 host receptors ACE2 and CD147 (BSG) are present on human oocytes and blastocysts. J Assist Reprod Genet. 37:2657–2660. 2020. View Article : Google Scholar : PubMed/NCBI

231 

Reis FM, Bouissou DR, Pereira VM, Camargos AF, dos Reis AM and Santos RA: Angiotensin-(1–7), its receptor Mas, and the angiotensin-converting enzyme type 2 are expressed in the human ovary. Fertil Steril. 95:176–181. 2011. View Article : Google Scholar : PubMed/NCBI

232 

Stanley KE, Thomas E, Leaver M and Wells D: Coronavirus disease-19 and fertility: Viral host entry protein expression in male and female reproductive tissues. Fertil Steril. 114:33–43. 2020. View Article : Google Scholar : PubMed/NCBI

233 

Domińska K: Involvement of ACE2/Ang-(1–7)/MAS1 axis in the regulation of ovarian function in mammals. Int J Mol Sci. 21:45722020. View Article : Google Scholar : PubMed/NCBI

234 

Nagappan A, Kim KH and Moon Y: Caveolin-1-ACE2 axis modulates xenobiotic metabolism-linked chemoresistance in ovarian clear cell carcinoma. Cell Biol Toxicol. 39:1181–1201. 2023. View Article : Google Scholar : PubMed/NCBI

235 

Delforce SJ, Lumbers ER, Corbisier de Meaultsart C, Wang Y, Proietto A, Otton G, Scurry J, Verrills NM, Scott RJ and Pringle KG: Expression of renin-angiotensin system (RAS) components in endometrial cancer. Endocr Connect. 6:9–19. 2017. View Article : Google Scholar : PubMed/NCBI

236 

Grzegrzolka J, Swiatko K, Pula B, Zamirska A, Olbromski M, Bieniek A, Szepietowski J, Rys J, Dziegiel P and Podhorska-Okolow M: ACE and ACE2 expression in normal and malignant skin lesions. Folia Histochem Cytobiol. 51:232–238. 2013. View Article : Google Scholar : PubMed/NCBI

237 

Siljee S, Pilkington T, Brasch HD, Bockett N, Patel J, Paterson E, Davis PF and Tan ST: Cancer stem cells in head and neck metastatic malignant melanoma express components of the renin-angiotensin system. Life (Basel). 10:2682020.PubMed/NCBI

238 

Ender SA, Dallmer A, Lässig F, Lendeckel U and Wolke C: Expression and function of the ACE2/angiotensin(1–7)/Mas axis in osteosarcoma cell lines U-2 OS and MNNG-HOS. Mol Med Rep. 10:804–810. 2014. View Article : Google Scholar : PubMed/NCBI

239 

Nehme A, Cerutti C, Dhaouadi N, Gustin MP, Courand PY, Zibara K and Bricca G: Atlas of tissue renin-angiotensin-aldosterone system in human: A transcriptomic meta-analysis. Sci Rep. 5:100352015. View Article : Google Scholar : PubMed/NCBI

240 

Haznedaroglu IC and Malkan UY: Local bone marrow renin-angiotensin system in the genesis of leukemia and other malignancies. Eur Rev Med Pharmacol Sci. 20:4089–4111. 2016.PubMed/NCBI

241 

Lin C, Datta V, Okwan-Duodu D, Chen X, Fuchs S, Alsabeh R, Billet S, Bernstein KE and Shen XZ: Angiotensin-converting enzyme is required for normal myelopoiesis. FASEB J. 25:1145–1155. 2011. View Article : Google Scholar : PubMed/NCBI

242 

Rodgers KE, Xiong S and diZerega GS: Accelerated recovery from irradiation injury by angiotensin peptides. Cancer Chemother Pharmacol. 49:403–411. 2002. View Article : Google Scholar : PubMed/NCBI

243 

Rodgers KE, Espinoza T, Roda N, Meeks CJ, Hill C, Louie SG and Dizerega GS: Accelerated hematopoietic recovery with angiotensin-(1–7) after total body radiation. Int J Radiat Biol. 88:466–476. 2012. View Article : Google Scholar : PubMed/NCBI

244 

Ratajczak MZ, Bujko K, Ciechanowicz A, Sielatycka K, Cymer M, Marlicz W and Kucia M: SARS-CoV-2 Entry receptor ACE2 is expressed on very small CD45-precursors of hematopoietic and endothelial cells and in response to virus spike protein activates the Nlrp3 inflammasome. Stem Cell Rev Rep. 17:266–277. 2021. View Article : Google Scholar : PubMed/NCBI

245 

Park TS and Zambidis ET: A role for the renin-angiotensin system in hematopoiesis. Haematologica. 94:745–747. 2009. View Article : Google Scholar : PubMed/NCBI

246 

Zambidis ET, Park TS, Yu W, Tam A, Levine M, Yuan X, Pryzhkova M and Péault B: Expression of angiotensin-converting enzyme (CD143) identifies and regulates primitive hemangioblasts derived from human pluripotent stem cells. Blood. 112:3601–3614. 2008. View Article : Google Scholar : PubMed/NCBI

247 

Uz B, Tatonyan SC, Sayitoglu M, Erbilgin Y, Ng OH, Buyukasik Y, Sayinalp N, Aksu S, Goker H, Ozcebe OI, et al: Local hematopoietic renin-angiotensin system in myeloid versus lymphoid hematological neoplastic disorders. J Renin Angiotensin Aldosterone Syst. 14:308–314. 2013. View Article : Google Scholar : PubMed/NCBI

248 

Teresa Gomez Casares M, de la Iglesia S, Perera M, Lemes A, Campo C, Gonzalez San Miguel JD, Bosch JM, Suarez A, Guerra L, Rodriguez-Peréz JC and Molero T: Renin expression in hematological malignancies and its role in the regulation of hematopoiesis. Leuk Lymphoma. 43:2377–2381. 2002. View Article : Google Scholar : PubMed/NCBI

249 

Alshareef A: Effect of SARS-CoV-2 entry factors on myeloid cancers. J Nippon Med Sch. 89:95–101. 2022. View Article : Google Scholar : PubMed/NCBI

250 

Kozako T and Soeda S, Yoshimitsu M, Arima N, Kuroki A, Hirata S, Tanaka H, Imakyure O, Tone N, Honda S and Soeda S: Angiotensin II type 1 receptor blocker telmisartan induces apoptosis and autophagy in adult T-cell leukemia cells. FEBS Open Bio. 6:442–460. 2016. View Article : Google Scholar : PubMed/NCBI

251 

Lima RS, Carvalho Rocha LP and Rocha Moreira P: Genetic and epigenetic control of ACE2 expression and its possible role in COVID-19. Cell Biochem Funct. 39:713–726. 2021. View Article : Google Scholar : PubMed/NCBI

252 

Dowell J, Bice Z, Yan K, Girija G and Konduri GG: Hyperoxia-induced airflow restriction and Renin-Angiotensin system expression in a bronchopulmonary dysplasia mouse model. Physiol Rep. 12:e158952024. View Article : Google Scholar : PubMed/NCBI

253 

Miroslavova Pencheva M and Nikolaeva Genova S: SARS-CoV-2 induced changes in the lungs based on autopsy cases. Indian J Pathol Microbiol. 66:19–23. 2023. View Article : Google Scholar : PubMed/NCBI

254 

Ulrich–Merzenich GS, Shcherbakova A, Pizarro C and Dirk Skowasch D: Dexamethasone, remdesivir and azithromycin modulate ACE2 and IL-6 in lung epithelial cells. Pneumologie. 79:134–140. 2025. View Article : Google Scholar : PubMed/NCBI

255 

Miura Y, Ohkubo H, Nakano A, Bourke JE and Kanazawa S: Pathophysiological conditions induced by SARS-CoV-2 infection reduce ACE2 expression in the lung. Front Immunol. 13:10286132022. View Article : Google Scholar : PubMed/NCBI

256 

Koehler VF, Knösel T, Hasmann SE, Scherer C, Hellmuth JC, Muenchhoff M, Munker SM, Hoster E, Ladurner R and Spitzweg C: Thyroidal Angiotensin-Converting enzyme 2 protein expression and thyroid function tests in patients with COVID-19: Results from a retrospective case series and a prospective cohort study. Thyroid. 33:177–185. 2023. View Article : Google Scholar : PubMed/NCBI

257 

Bronowicka–Szydełko A, Rabczyński M, Dumas I, Fiodorenko-Dumas Z, Wojtczak B, Kotyra L, Kustrzeba–Wójcicka I, Lewandowski L, Ponikowska B, Kuzan A, et al: State of knowledge about thyroid cancers in the era of COVID-19-A narrative review. Biomedicines. 12:28292024. View Article : Google Scholar : PubMed/NCBI

258 

Serwaa A, Oyawoye F, Amoakoh Owusu I, Dosoo D, Adom Manu A, Kojo Sobo A, Fosu K, Ochieng Olwal C, Kojo Quashie P and Rosebud Aikins A: In vitro analysis suggests that SARS-CoV-2 infection differentially modulates cancer-like phenotypes and cytokine expression in colorectal and prostate cancer cells. Sci Rep. 14:246252024. View Article : Google Scholar : PubMed/NCBI

259 

Shirazi M, Cianfarini C, Ismail A, Wysocki J, Wang JJ, Ye M, Zhang ZJ and Batlle D: Altered kidney distribution and loss of ACE2 into the urine in acute kidney injury. Am J Physiol Renal Physiol. 327:F412–F425. 2024. View Article : Google Scholar : PubMed/NCBI

260 

Sanad AM, Qadri F, Popova E, Rodrigues AF, Heinbokel T, Quach S, Schulz A, Bachmann S, Kreutz R, Alenina N and Bader M: Transgenic angiotensin-converting enzyme 2 overexpression in the rat vasculature protects kidneys from ageing-induced injury. Kidney Int. 104:293–304. 2023. View Article : Google Scholar : PubMed/NCBI

261 

Rago V, Bossio S, Lofaro D, Perri A and Di Agostino S: New insights into the link between SARS-CoV-2 infection and renal cancer. Life (Basel). 14:522023.PubMed/NCBI

262 

Singh Parmar H, Nayak A, Kumar Gavel P, Chandra Jha H, Bhagwat S and Sharma R: Cross talk between COVID-19 and breast cancer. Curr Cancer Drug Targets. 21:575–600. 2021. View Article : Google Scholar : PubMed/NCBI

263 

Sinha S, Cheng K, Schäffer AA, Aldape K, Schiff E and Ruppin E: In vitro and in vivo identification of clinically approved drugs that modify ACE2 expression. Mol Syst Biol. 16:e96282020. View Article : Google Scholar : PubMed/NCBI

264 

Beacon TH, Delcuve GP and Davie JR: Epigenetic regulation of ACE2, the receptor of the SARS-CoV-2 virus. Genome. 64:386–399. 2021. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Rizopoulos T and Assimakopoulou M: Angiotensin‑converting enzyme 2 expression in human tumors: Implications for prognosis and therapy (Review). Oncol Rep 54: 101, 2025.
APA
Rizopoulos, T., & Assimakopoulou, M. (2025). Angiotensin‑converting enzyme 2 expression in human tumors: Implications for prognosis and therapy (Review). Oncology Reports, 54, 101. https://doi.org/10.3892/or.2025.8934
MLA
Rizopoulos, T., Assimakopoulou, M."Angiotensin‑converting enzyme 2 expression in human tumors: Implications for prognosis and therapy (Review)". Oncology Reports 54.3 (2025): 101.
Chicago
Rizopoulos, T., Assimakopoulou, M."Angiotensin‑converting enzyme 2 expression in human tumors: Implications for prognosis and therapy (Review)". Oncology Reports 54, no. 3 (2025): 101. https://doi.org/10.3892/or.2025.8934
Copy and paste a formatted citation
x
Spandidos Publications style
Rizopoulos T and Assimakopoulou M: Angiotensin‑converting enzyme 2 expression in human tumors: Implications for prognosis and therapy (Review). Oncol Rep 54: 101, 2025.
APA
Rizopoulos, T., & Assimakopoulou, M. (2025). Angiotensin‑converting enzyme 2 expression in human tumors: Implications for prognosis and therapy (Review). Oncology Reports, 54, 101. https://doi.org/10.3892/or.2025.8934
MLA
Rizopoulos, T., Assimakopoulou, M."Angiotensin‑converting enzyme 2 expression in human tumors: Implications for prognosis and therapy (Review)". Oncology Reports 54.3 (2025): 101.
Chicago
Rizopoulos, T., Assimakopoulou, M."Angiotensin‑converting enzyme 2 expression in human tumors: Implications for prognosis and therapy (Review)". Oncology Reports 54, no. 3 (2025): 101. https://doi.org/10.3892/or.2025.8934
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