Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Oncology Letters
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-1074 Online ISSN: 1792-1082
Journal Cover
November-2024 Volume 28 Issue 5

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
November-2024 Volume 28 Issue 5

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Review Open Access

Cystine/cysteine metabolism regulates the progression and response to treatment of triple‑negative breast cancer (Review)

  • Authors:
    • Wanting Xiao
    • Chaoyang Xu
  • View Affiliations / Copyright

    Affiliations: Department of Breast and Thyroid Surgery, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, Zhejiang 321000, P.R. China
    Copyright: © Xiao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 521
    |
    Published online on: August 30, 2024
       https://doi.org/10.3892/ol.2024.14654
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Breast cancer is the most prevalent neoplasm affecting women globally, of which a notable proportion of cases are triple‑negative breast cancer (TNBC). However, there are limited curative treatment options for patients with TNBC, despite advancements in the field. Amino acids and amino acid transporters serve vital roles in the regulation of tumor metabolism. Notably, cystine and cysteine can interconvert via a redox reaction, with cysteine exerting control on cell survival and growth and exogenous cystine serving a crucial role in the proliferation of numerous types of cancers. Breast cancer has been reported to disrupt the cystine/cysteine metabolism pathway, as cystine and cysteine transporters affect the development and growth of tumors. The present review aims to provide a comprehensive overview of the metabolic pathways involving cystine and cysteine in normal and TNBC cells. Furthermore, the roles of cystine and cysteine transporters in TNBC progression and metastasis and their potential as therapeutic targets for treatment of TNBC are evaluated.
View Figures

Figure 1

Figure 2

View References

1 

Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A and Bray F: Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 71:209–249. 2021. View Article : Google Scholar : PubMed/NCBI

2 

Morris GJ, Naidu S, Topham AK, Guiles F, Xu Y, McCue P, Schwartz GF, Park PK, Rosenberg AL, Brill K and Mitchell EP: Differences in breast carcinoma characteristics in newly diagnosed African-American and Caucasian patients: A single-institution compilation compared with the National Cancer Institute's Surveillance, Epidemiology, and End Results database. Cancer. 110:876–884. 2007. View Article : Google Scholar : PubMed/NCBI

3 

Singh DD and Yadav DK: TNBC: Potential targeting of multiple receptors for a therapeutic breakthrough, nanomedicine, and immunotherapy. Biomedicines. 9:8762021. View Article : Google Scholar : PubMed/NCBI

4 

Dietze EC, Sistrunk C, Miranda-Carboni G, O'Regan R and Seewaldt VL: Triple-negative breast cancer in African-American women: Disparities versus biology. Nat Rev Cancer. 15:248–254. 2015. View Article : Google Scholar : PubMed/NCBI

5 

Gandhi N and Das GM: Metabolic reprogramming in breast cancer and its therapeutic implications. Cells. 8:892019. View Article : Google Scholar : PubMed/NCBI

6 

Litton JK, Rugo HS, Ettl J, Hurvitz SA, Gonçalves A, Lee KH, Fehrenbacher L, Yerushalmi R, Mina LA, Martin M, et al: Talazoparib in patients with advanced breast cancer and a germline BRCA mutation. N Engl J Med. 379:753–763. 2018. View Article : Google Scholar : PubMed/NCBI

7 

Wang Z, Jiang Q and Dong C: Metabolic reprogramming in triple-negative breast cancer. Cancer Biol Med. 17:44–59. 2020. View Article : Google Scholar : PubMed/NCBI

8 

Nedeljković M and Damjanović A: Mechanisms of chemotherapy resistance in triple-negative breast cancer-how we can rise to the challenge. Cells. 8:9572019. View Article : Google Scholar : PubMed/NCBI

9 

Pavlova NN, Zhu J and Thompson CB: The hallmarks of cancer metabolism: Still emerging. Cell Metab. 34:355–377. 2022. View Article : Google Scholar : PubMed/NCBI

10 

DeBerardinis RJ, Lum JJ, Hatzivassiliou G and Thompson CB: The biology of cancer: Metabolic reprogramming fuels cell growth and proliferation. Cell Metab. 7:11–20. 2008. View Article : Google Scholar : PubMed/NCBI

11 

Tang X, Lin CC, Spasojevic I, Iversen ES, Chi JT and Marks JR: A joint analysis of metabolomics and genetics of breast cancer. Breast Cancer Res. 16:4152014. View Article : Google Scholar : PubMed/NCBI

12 

Wei Z, Liu X, Cheng C, Yu W and Yi P: Metabolism of amino acids in cancer. Front Cell Dev Biol. 8:6038372021. View Article : Google Scholar : PubMed/NCBI

13 

Sheen JH, Zoncu R, Kim D and Sabatini DM: Defective regulation of autophagy upon leucine deprivation reveals a targetable liability of human melanoma cells in vitro and in vivo. Cancer Cell. 19:613–628. 2011. View Article : Google Scholar : PubMed/NCBI

14 

Tang X, Wu J, Ding CK, Lu M, Keenan MM, Lin CC, Lin CA, Wang CC, George D, Hsu DS and Chi JT: Cystine deprivation triggers programmed necrosis in VHL-Deficient renal cell carcinomas. Cancer Res. 76:1892–1903. 2016. View Article : Google Scholar : PubMed/NCBI

15 

Iglehart J, York RM, Modest AP, Lazarus H and Livingston D: Cystine requirement of continuous human lymphoid cell lines of normal and leukemic origin. J Biol Chem. 252:7184–7191. 1977. View Article : Google Scholar : PubMed/NCBI

16 

Edwards DN, Ngwa VM, Raybuck AL, Wang S, Hwang Y, Kim LC, Cho SH, Paik Y, Wang Q, Zhang S, et al: Selective glutamine metabolism inhibition in tumor cells improves antitumor T lymphocyte activity in triple-negative breast cancer. J Clin Invest. 131:e1401002021. View Article : Google Scholar : PubMed/NCBI

17 

Zhang W, Trachootham D, Liu J, Chen G, Pelicano H, Garcia-Prieto C, Lu W, Burger JA, Croce CM, Plunkett W, et al: Stromal control of cystine metabolism promotes cancer cell survival in chronic lymphocytic leukaemia. Nat Cell Biol. 14:276–286. 2012. View Article : Google Scholar : PubMed/NCBI

18 

Daher B, Vučetić M and Pouysségur J: Cysteine depletion, a key action to challenge cancer cells to ferroptotic cell death. Front Oncol. 10:7232020. View Article : Google Scholar : PubMed/NCBI

19 

Stipanuk MH: Sulfur amino acid metabolism: Pathways for production and removal of homocysteine and cysteine. Annu Rev Nutr. 24:539–577. 2004. View Article : Google Scholar : PubMed/NCBI

20 

Zhang HF, Klein Geltink RI, Parker SJ and Sorensen PH: Transsulfuration, minor player or crucial for cysteine homeostasis in cancer. Trends Cell Biol. 32:800–814. 2022. View Article : Google Scholar : PubMed/NCBI

21 

Combs JA and DeNicola GM: The non-essential amino acid cysteine becomes essential for tumor proliferation and survival. Cancers (Basel). 11:6782019. View Article : Google Scholar : PubMed/NCBI

22 

Zhu J, Berisa M, Schwörer S, Qin W, Cross JR and Thompson CB: Transsulfuration activity can support cell growth upon extracellular cysteine limitation. Cell Metab. 30:865–876.e5. 2019. View Article : Google Scholar : PubMed/NCBI

23 

Lien EC, Ghisolfi L, Geck RC, Asara JM and Toker A: Oncogenic PI3K promotes methionine dependency in breast cancer cells through the cystine-glutamate antiporter xCT. Sci Signal. 10:eaao66042017. View Article : Google Scholar : PubMed/NCBI

24 

Pajares MA and Perez-Sala D: Mammalian sulfur amino acid metabolism: A nexus between redox regulation, nutrition, epigenetics, and detoxification. Antioxid Redox Signal. 29:408–452. 2018. View Article : Google Scholar : PubMed/NCBI

25 

Yin L, Duan JJ, Bian XW and Yu SC: Triple-negative breast cancer molecular subtyping and treatment progress. Breast Cancer Res. 22:612020. View Article : Google Scholar : PubMed/NCBI

26 

Prat A, Parker JS, Karginova O, Fan C, Livasy C, Herschkowitz JI, He X and Perou CM: Phenotypic and molecular characterization of the claudin-low intrinsic subtype of breast cancer. Breast Cancer Res. 12:R682010. View Article : Google Scholar : PubMed/NCBI

27 

Tang X, Ding CK, Wu J, Sjol J, Wardell S, Spasojevic I, George D, McDonnell DP, Hsu DS, Chang JT and Chi JT: Cystine addiction of triple-negative breast cancer associated with EMT augmented death signaling. Oncogene. 36:4235–4242. 2016. View Article : Google Scholar : PubMed/NCBI

28 

Chen MS, Wang SF, Hsu CY, Yin PH, Yeh TS, Lee HC and Tseng LM: CHAC1 degradation of glutathione enhances cystine-starvation-induced necroptosis and ferroptosis in human triple negative breast cancer cells via the GCN2-eIF2α-ATF4 pathway. Oncotarget. 8:114588–114602. 2017. View Article : Google Scholar : PubMed/NCBI

29 

Shibue T and Weinberg RA: EMT, CSCs, and drug resistance: The mechanistic link and clinical implications. Nat Rev Clin Oncol. 14:611–629. 2017. View Article : Google Scholar : PubMed/NCBI

30 

Lin J, Lee IM, Song Y, Cook NR, Selhub J, Manson JE, Buring JE and Zhang SM: Plasma homocysteine and cysteine and risk of breast cancer in women. Cancer Res. 70:2397–2405. 2010. View Article : Google Scholar : PubMed/NCBI

31 

Wu LL and Wu JT: Hyperhomocysteinemia is a risk factor for cancer and a new potential tumor marker. Clin Chim Acta. 322:21–28. 2002. View Article : Google Scholar : PubMed/NCBI

32 

Sun CF, Haven TR, Wu TL, Tsao KC and Wu JT: Serum total homocysteine increases with the rapid proliferation rate of tumor cells and decline upon cell death: A potential new tumor marker. Clin Chim Acta. 321:55–62. 2002. View Article : Google Scholar : PubMed/NCBI

33 

Xue F and Michels KB: Diabetes, metabolic syndrome, and breast cancer: A review of the current evidence. Am J Clin Nutr. 86:S823–S835. 2007. View Article : Google Scholar : PubMed/NCBI

34 

La Vecchia C, Giordano SH, Hortobagyi GN and Chabner B: Overweight, obesity, diabetes, and risk of breast cancer: Interlocking pieces of the puzzle. Oncologist. 16:726–729. 2011. View Article : Google Scholar : PubMed/NCBI

35 

Lewerenz J, Hewett SJ, Huang Y, Lambros M, Gout PW, Kalivas PW, Massie A, Smolders I, Methner A, Pergande M, et al: The Cystine/Glutamate Antiporter System xc-in Health and disease: From molecular mechanisms to novel therapeutic opportunities. Antioxid Redox Signa. 18:522–555. 2013. View Article : Google Scholar : PubMed/NCBI

36 

Sato H, Tamba M, Ishii T and Bannai S: Cloning and expression of a plasma membrane cystine/glutamate exchange transporter composed of two distinct proteins. J Biol Chem. 274:11455–11458. 1999. View Article : Google Scholar : PubMed/NCBI

37 

Koppula P, Zhuang L and Gan B: Cystine transporter SLC7A11/xCT in cancer: Ferroptosis, nutrient dependency, and cancer therapy. Protein Cell. 12:599–620. 2020. View Article : Google Scholar : PubMed/NCBI

38 

Kandasamy P, Gyimesi G, Kanai Y and Hediger MA: Amino acid transporters revisited: New views in health and disease. Trends Biochem Sci. 43:752–789. 2018. View Article : Google Scholar : PubMed/NCBI

39 

Miyazaki I, Murakami S, Torigoe N, Kitamura Y and Asanuma M: Neuroprotective effects of levetiracetam target xCT in astrocytes in parkinsonian mice. J Neurochem. 136:194–204. 2015. View Article : Google Scholar : PubMed/NCBI

40 

Sugano K, Maeda K, Ohtani H, Nagahara H, Shibutani M and Hirakawa K: Expression of xCT as a predictor of disease recurrence in patients with colorectal cancer. Anticancer Res. 35:677–682. 2015.PubMed/NCBI

41 

Robert SM, Buckingham SC, Campbell SL, Robel S, Holt KT, Ogunrinu-Babarinde T, Warren PP, White DM, Reid MA, Eschbacher JM, et al: SLC7A11 expression is associated with seizures and predicts poor survival in patients with malignant glioma. Sci Transl Med. 7:289ra862015. View Article : Google Scholar : PubMed/NCBI

42 

Ji X, Qian J, Rahman SMJ, Siska PJ, Zou Y, Harris BK, Hoeksema MD, Trenary IA, Heidi C, Eisenberg R, et al: xCT (SLC7A11)-mediated metabolic reprogramming promotes non-small cell lung cancer progression. Oncogene. 37:5007–5019. 2018. View Article : Google Scholar : PubMed/NCBI

43 

Ruiu R, Rolih V, Bolli E, Barutello G, Riccardo F, Quaglino E, Merighi IF, Pericle F, Donofrio G, Cavallo F and Conti L: Fighting breast cancer stem cells through the immune-targeting of the xCT cystine-glutamate antiporter. Cancer Immunol Immunother. 68:131–141. 2019. View Article : Google Scholar : PubMed/NCBI

44 

Lanzardo S, Conti L, Rooke R, Ruiu R, Accart N, Bolli E, Arigoni M, Macagno M, Barrera G, Pizzimenti S, et al: Immunotargeting of antigen xCT attenuates Stem-like cell behavior and metastatic progression in breast cancer. Cancer Res. 76:62–72. 2016. View Article : Google Scholar : PubMed/NCBI

45 

Timmerman LA, Holton T, Yuneva M, Louie RJ, Padró M, Daemen A, Hu M, Chan DA, Ethier SP, van't Veer LJ, et al: Glutamine sensitivity analysis identifies the xCT antiporter as a common triple-negative breast tumor therapeutic target. Cancer Cell. 24:450–465. 2013. View Article : Google Scholar : PubMed/NCBI

46 

Hasegawa M, Takahashi H, Rajabi H, Alam M, Suzuki Y, Yin L, Tagde A, Maeda T, Hiraki M, Sukhatme VP, et al: Functional interactions of the cystine/glutamate antiporter, CD44v and MUC1-C oncoprotein in triple-negative breast cancer cells. Oncotarget. 7:11756–11769. 2016. View Article : Google Scholar : PubMed/NCBI

47 

Ishimoto T, Nagano O, Yae T, Tamada M, Motohara T, Oshima H, Oshima M, Ikeda T, Asaba R, Yagi H, et al: CD44 variant regulates redox status in cancer cells by stabilizing the xCT subunit of system xc- and thereby promotes tumor growth. Cancer Cell. 19:387–400. 2011. View Article : Google Scholar : PubMed/NCBI

48 

Fotiadis D, Kanai Y and Palacín M: The SLC3 and SLC7 families of amino acid transporters. Mol Aspects Med. 34:139–158. 2013. View Article : Google Scholar : PubMed/NCBI

49 

Jiang Y, Cao Y, Wang Y, Li W, Liu X, Lv Y, Li X and Mi J: Cysteine transporter SLC3A1 promotes breast cancer tumorigenesis. Theranostics. 7:1036–1046. 2017. View Article : Google Scholar : PubMed/NCBI

50 

Jeong JY, Oh KJ, Sohn JS, Jun DY, Shin JI, Lee KH and Lee JY: Clinical course and mutational analysis of patients with cystine stone: A Single-Center experience. Biomedicines. 11:27472023. View Article : Google Scholar : PubMed/NCBI

51 

Trachootham D, Alexandre J and Huang P: Targeting cancer cells by ROS-mediated mechanisms: A radical therapeutic approach? Nat Rev Drug Discov. 8:579–591. 2009. View Article : Google Scholar : PubMed/NCBI

52 

Chio C II and Tuveson DA: ROS in cancer: The burning question. Trends Mol Med. 23:411–429. 2017. View Article : Google Scholar : PubMed/NCBI

53 

Haraguchi N, Inoue H, Tanaka F, Mimori K, Utsunomiya T, Sasaki A and Mori M: Cancer stem cells in human gastrointestinal cancers. Hum Cell. 19:24–29. 2006. View Article : Google Scholar : PubMed/NCBI

54 

Tarragó-Celada J, Foguet C, Tarrado-Castellarnau M, Marin S, Hernández-Alias X, Perarnau J, Morrish F, Hockenbery D, Gomis RR, Ruppin E, et al: Cysteine and folate metabolism are targetable vulnerabilities of metastatic colorectal cancer. Cancers (Basel). 13:4252021. View Article : Google Scholar : PubMed/NCBI

55 

Bao WEI, Han Q, Guan X, Wang Z and Gu MIN: Solute carrier-related signature for assessing prognosis and immunity in patients with clear-cell renal cell carcinoma. Oncol Res. 31:181–192. 2023. View Article : Google Scholar : PubMed/NCBI

56 

Cha YJ, Kim ES and Koo JS: Amino acid transporters and glutamine metabolism in breast cancer. Int J Mol Sci. 19:9072018. View Article : Google Scholar : PubMed/NCBI

57 

Todorova VK, Kaufmann Y, Luo S and Klimberg VS: Tamoxifen and raloxifene suppress the proliferation of estrogen receptor-negative cells through inhibition of glutamine uptake. Cancer Chemother Pharmacol. 67:285–291. 2011. View Article : Google Scholar : PubMed/NCBI

58 

Bernhardt S, Bayerlová M, Vetter M, Wachter A, Mitra D, Hanf V, Lantzsch T, Uleer C, Peschel S, John J, et al: Proteomic profiling of breast cancer metabolism identifies SHMT2 and ASCT2 as prognostic factors. Breast Cancer Res. 19:1122017. View Article : Google Scholar : PubMed/NCBI

59 

Jeon YJ, Khelifa S, Ratnikov B, Scott DA, Feng Y, Parisi F, Ruller C, Lau E, Kim H, Brill LM, et al: Regulation of glutamine carrier proteins by RNF5 determines breast cancer response to ER Stress-Inducing chemotherapies. Cancer Cell. 27:354–369. 2015. View Article : Google Scholar : PubMed/NCBI

60 

Sayin VI, Ibrahim MX, Larsson E, Nilsson JA, Lindahl P and Bergo MO: Antioxidants accelerate lung cancer progression in mice. Sci Transl Med. 6:221ra152014. View Article : Google Scholar : PubMed/NCBI

61 

Kennecke H, Yerushalmi R, Woods R, Cheang MCU, Voduc D, Speers CH, Nielsen TO and Gelmon K: Metastatic behavior of breast cancer subtypes. J Clin Oncol. 28:3271–3277. 2010. View Article : Google Scholar : PubMed/NCBI

62 

Weigelt B and Reis-Filho JS: Histological and molecular types of breast cancer: Is there a unifying taxonomy? Nat Rev Clin Oncol. 6:718–730. 2009. View Article : Google Scholar : PubMed/NCBI

63 

Sato R, Nakano T, Hosonaga M, Sampetrean O, Harigai R, Sasaki T, Koya I, Okano H, Kudoh J, Saya H and Arima Y: RNA sequencing analysis reveals interactions between breast cancer or melanoma cells and the tissue microenvironment during brain metastasis. Biomed Res Int. 2017:80329102017. View Article : Google Scholar : PubMed/NCBI

64 

Hosonaga M, Saya H and Arima Y: Molecular and cellular mechanisms underlying brain metastasis of breast cancer. Cancer Metastasis Rev. 39:711–720. 2020. View Article : Google Scholar : PubMed/NCBI

65 

Ruiu R, Cossu C, Iacoviello A, Conti L, Bolli E, Ponzone L, Magri J, Rumandla A, Calautti E and Cavallo F: Cystine/glutamate antiporter xCT deficiency reduces metastasis without impairing immune system function in breast cancer mouse models. J Exp Clin Cancer Res. 42:2542023. View Article : Google Scholar : PubMed/NCBI

66 

Hu J, Li G, Zhang P, Zhuang X and Hu G: A CD44v+ subpopulation of breast cancer stem-like cells with enhanced lung metastasis capacity. Cell Death Dis. 8:e26792017. View Article : Google Scholar : PubMed/NCBI

67 

Lollini PL, Cavallo F, Giovanni CD and Nanni P: Preclinical vaccines against mammary carcinoma. Expert Rev Vaccines. 12:1449–1463. 2013. View Article : Google Scholar : PubMed/NCBI

68 

Nagano O, Okazaki S and Saya H: Redox regulation in stem-like cancer cells by CD44 variant isoforms. Oncogene. 32:5191–5198. 2013. View Article : Google Scholar : PubMed/NCBI

69 

Kinoshita H, Okabe H, Beppu T, Chikamoto A, Hayashi H, Imai K, Mima K, Nakagawa S, Ishimoto T, Miyake K, et al: Cystine/glutamic acid transporter is a novel marker for predicting poor survival in patients with hepatocellular carcinoma. Oncol Rep. 29:685–689. 2013. View Article : Google Scholar : PubMed/NCBI

70 

Dixon SJ, Lemberg KM, Lamprecht MR, Skouta R, Zaitsev EM, Gleason CE, Patel DN, Bauer AJ, Cantley AM, Yang WS, et al: Ferroptosis: An Iron-dependent form of nonapoptotic cell death. Cell. 149:1060–1072. 2012. View Article : Google Scholar : PubMed/NCBI

71 

Hassannia B, Vandenabeele P and Vanden Berghe T: Targeting ferroptosis to iron out cancer. Cancer Cell. 35:830–849. 2019. View Article : Google Scholar : PubMed/NCBI

72 

Xu T, Ding W, Ji X, Ao X, Liu Y, Yu W and Wang J: Molecular mechanisms of ferroptosis and its role in cancer therapy. J Cell Mol Med. 23:4900–4912. 2019. View Article : Google Scholar : PubMed/NCBI

73 

Zhang Y, Tan H, Daniels JD, Zandkarimi F, Liu H, Brown LM, Uchida K, O'Connor OA and Stockwell BR: Imidazole ketone erastin induces ferroptosis and slows tumor growth in a mouse lymphoma model. Cell Chem Biol. 26:623–633.e9. 2019. View Article : Google Scholar : PubMed/NCBI

74 

Zheng YW, Miao XY, Xiong L, Chen B, Kong FH, Zhou JJ, Liu ZT, Wen Y, Zhang ZJ and Zou H: Sulfasalazine sensitizes polyhematoporphyrin-mediated photodynamic therapy in cholangiocarcinoma by targeting xCT. Front Pharmacol. 12:7234882021. View Article : Google Scholar : PubMed/NCBI

75 

Yu H, Hu K, Zhang T and Ren H: Identification of target genes related to sulfasalazine in triple-negative breast cancer through Network pharmacology. Med Sci Monit. 26:e9265502020. View Article : Google Scholar : PubMed/NCBI

76 

Gout P, Buckley A, Simms C and Bruchovsky N: Sulfasalazine, a potent suppressor of lymphoma growth by inhibition of the x(c)-cystine transporter: A new action for an old drug. Leukemia. 15:1633–1640. 2001. View Article : Google Scholar : PubMed/NCBI

77 

Guan J, Lo M, Dockery P, Mahon S, Karp CM, Buckley AR, Lam S, Gout PW and Wang YZ: The × c-cystine/glutamate antiporter as a potential therapeutic target for small-cell lung cancer: Use of sulfasalazine. Cancer Chemother Pharmacol. 64:463–472. 2009. View Article : Google Scholar : PubMed/NCBI

78 

Doxsee DW, Gout PW, Kurita T, Lo M, Buckley AR, Wang Y, Xue H, Karp CM, Cutz JC, Cunha GR and Wang YZ: Sulfasalazine-induced cystine starvation: Potential use for prostate cancer therapy. Prostate. 67:162–171. 2007. View Article : Google Scholar : PubMed/NCBI

79 

Shitara K, Doi T, Nagano O, Imamura CK, Ozeki T, Ishii Y, Tsuchihashi K, Takahashi S, Nakajima TE, Hironaka S, et al: Dose-escalation study for the targeting of CD44v+ cancer stem cells by sulfasalazine in patients with advanced gastric cancer (EPOC1205). Gastric Cancer. 20:341–349. 2017. View Article : Google Scholar : PubMed/NCBI

80 

Shitara K, Doi T, Nagano O, Fukutani M, Hasegawa H, Nomura S, Sato A, Kuwata T, Asai K, Einaga Y, et al: Phase 1 study of sulfasalazine and cisplatin for patients with CD44v-positive gastric cancer refractory to cisplatin (EPOC1407). Gastric Cancer. 20:1004–1009. 2017. View Article : Google Scholar : PubMed/NCBI

81 

Otsubo K, Nosaki K, Imamura CK, Ogata H, Fujita A, Sakata S, Hirai F, Toyokawa G, Iwama E, Harada T, et al: Phase I study of salazosulfapyridine in combination with cisplatin and pemetrexed for advanced non-small-cell lung cancer. Cancer Sci. 108:1843–189. 2017. View Article : Google Scholar : PubMed/NCBI

82 

Dai Z, Huang Y, Sadee W and Blower P: Chemoinformatics analysis identifies cytotoxic compounds susceptible to chemoresistance mediated by glutathione and cystine/glutamate transport system xc-. J Med Chem. 50:1896–1906. 2007. View Article : Google Scholar : PubMed/NCBI

83 

Narang VS, Pauletti GM, Gout PW, Buckley DJ and Buckley AR: Sulfasalazine-induced reduction of glutathione levels in breast cancer cells: Enhancement of growth-inhibitory activity of doxorubicin. Chemotherapy. 53:210–217. 2007. View Article : Google Scholar : PubMed/NCBI

84 

Barutello G, Di Lorenzo A, Gasparetto A, Galiazzi C, Bolli E, Conti L and Cavallo F: Immunotherapy against the Cystine/Glutamate Antiporter xCT improves the efficacy of APR-246 in preclinical breast cancer models. Biomedicines. 10:28432022. View Article : Google Scholar : PubMed/NCBI

85 

Conti L, Bolli E, Di Lorenzo A, Franceschi V, Macchi F, Riccardo F, Ruiu R, Russo L, Quaglino E, Donofrio G and Cavallo F: Immunotargeting of the xCT Cystine/Glutamate antiporter potentiates the efficacy of HER2-targeted immunotherapies in breast cancer. Cancer Immunol Res. 8:1039–53. 2020. View Article : Google Scholar : PubMed/NCBI

86 

Yu H, Yang C, Jian L, Guo S, Chen R, Li K, Qu F, Tao K, Fu Y, Luo F and Liu S: Sulfasalazine-induced ferroptosis in breast cancer cells is reduced by the inhibitory effect of estrogen receptor on the transferrin receptor. Oncol Rep. 42:826–838. 2019.PubMed/NCBI

87 

Sehm T, Rauh M, Wiendieck K, Buchfelder M, Eyüpoglu IY and Savaskan NE: Temozolomide toxicity operates in a xCT/SLC7a11 dependent manner and is fostered by ferroptosis. Oncotarget. 7:746302016. View Article : Google Scholar : PubMed/NCBI

88 

Wei CW, Yu YL, Lu JY, Hung YT, Liu HC and Yiang GT: Anti-cancer effects of sulfasalazine and Vitamin E succinate in MDA-MB 231 Triple-negative breast cancer cells. Int J Med Sci. 16:494–500. 2019. View Article : Google Scholar : PubMed/NCBI

89 

Verbruggen L, Sprimont L, Bentea E, Janssen P, Gharib A, Deneyer L, De Pauw L, Lara O, Sato H, Nicaise C and Massie A: Chronic sulfasalazine treatment in mice induces system xc−-Independent adverse effects. Front Pharmacol. 12:6256992021. View Article : Google Scholar : PubMed/NCBI

90 

Robe PA, Martin DH, Nguyen-Khac MT, Artesi M, Deprez M, Albert A, Vanbelle S, Califice S, Bredel M and Bours V: Early termination of ISRCTN45828668, a phase 1/2 prospective, randomized study of sulfasalazine for the treatment of progressing malignant gliomas in adults. BMC Cancer. 9:3722009. View Article : Google Scholar : PubMed/NCBI

91 

Donofrio G, Tebaldi G, Lanzardo S, Ruiu R, Bolli E, Ballatore A, Rolih V, Macchi F, Conti L and Cavallo F: Bovine herpesvirus 4-based vector delivering the full length xCT DNA efficiently protects mice from mammary cancer metastases by targeting cancer stem cells. Oncoimmunology. 7:e14941082018. View Article : Google Scholar : PubMed/NCBI

92 

Wang F and Yang Y: Suppression of the xCT-CD44v antiporter system sensitizes triple-negative breast cancer cells to doxorubicin. Breast Cancer Res Treat. 147:203–210. 2014. View Article : Google Scholar : PubMed/NCBI

93 

Marin-Acevedo JA, Soyano AE, Dholaria B, Knutson KL and Lou Y: Cancer immunotherapy beyond immune checkpoint inhibitors. J Hematol Oncol. 11:82018. View Article : Google Scholar : PubMed/NCBI

94 

Ruzzi F, Semprini MS, Scalambra L, Palladini A, Angelicola S, Cappello C, Pittino OM, Nanni P and Lollini PL: Virus-like particle (VLP) vaccines for cancer immunotherapy. Int J Mol Sci. 24:129632023. View Article : Google Scholar : PubMed/NCBI

95 

Rolih V, Caldeira J, Bolli E, Salameh A, Conti L, Barutello G, Riccardo F, Magri J, Lamolinara A, Parra K, et al: Development of a VLP-based vaccine displaying an xCT extracellular domain for the treatment of metastatic breast cancer. Cancers. 12:14922020. View Article : Google Scholar : PubMed/NCBI

96 

Bolli E, O'Rourke JP, Conti L, Lanzardo S, Rolih V, Christen JM, Barutello G, Forni M, Pericle F and Cavallo F: A Virus-Like-Particle immunotherapy targeting Epitope-specific anti-xCT expressed on cancer stem cell inhibits the progression of metastatic cancer in vivo. Oncoimmunology. 7:e14087462018. View Article : Google Scholar : PubMed/NCBI

97 

Lopes A, Vandermeulen G and Preat V: Cancer DNA vaccines: Current preclinical and clinical developments and future perspectives. J Exp Clin Cancer Res. 38:1462019. View Article : Google Scholar : PubMed/NCBI

98 

Kraft VAN, Bezjian CT, Pfeiffer S, Ringelstetter L, Müller C, Zandkarimi F, Merl-Pham J, Bao X, Anastasov N, Kössl J, et al: GTP cyclohydrolase 1/Tetrahydrobiopterin counteract ferroptosis through lipid remodeling. ACS Cent Sci. 6:41–53. 2019. View Article : Google Scholar : PubMed/NCBI

99 

Yang WS, SriRamaratnam R, Welsch ME, Shimada K, Skouta R, Viswanathan VS, Cheah JH, Clemons PA, Shamji AF, Clish CB, et al: Regulation of ferroptotic cancer cell death by GPX4. Cell. 156:317–331. 2014. View Article : Google Scholar : PubMed/NCBI

100 

Imai H, Matsuoka M, Kumagai T, Sakamoto T and Koumura T: Lipid Peroxidation-dependent cell death regulated by GPx4 and ferroptosis. Curr Top Microbiol Immunol. 403:143–170. 2017.PubMed/NCBI

101 

Lv Y, Liang C, Sun Q, Zhu J, Xu H, Li X, Li X, Li YY, Wang Q, Yuan H, et al: Structural insights into FSP1 catalysis and ferroptosis inhibition. Nat Commun. 14:59332023. View Article : Google Scholar : PubMed/NCBI

102 

Bersuker K, Hendricks JM, Li Z, Magtanong L, Ford B, Tang PH, Roberts MA, Tong B, Maimone TJ, Zoncu R, et al: The CoQ oxidoreductase FSP1 acts parallel to GPX4 to inhibit ferroptosis. Nature. 575:688–692. 2019. View Article : Google Scholar : PubMed/NCBI

103 

Mao C, Liu X, Zhang Y, Lei G, Yan Y, Lee H, Koppula P, Wu S, Zhuang L, Fang B, et al: DHODH-mediated ferroptosis defence is a targetable vulnerability in cancer. Nature. 593:586–590. 2021. View Article : Google Scholar : PubMed/NCBI

104 

Harris IS, Endress JE, Coloff JL, Selfors LM, McBrayer SK, Rosenbluth JM, Takahashi N, Dhakal S, Koduri V, Oser MG, et al: Deubiquitinases maintain protein homeostasis and survival of cancer cells upon glutathione depletion. Cell Metab. 29:1166–1181.e6. 2019. View Article : Google Scholar : PubMed/NCBI

105 

Shin D, Lee J, You JH, Kim D and Roh JL: Dihydrolipoamide dehydrogenase regulates cystine deprivation-induced ferroptosis in head and neck cancer. Redox Biol. 30:1014182020. View Article : Google Scholar : PubMed/NCBI

106 

Ensink EJT, Medeiros HCD, Thurston G, Pardal A, Yu L and Lunt SY: Pyruvate kinase activity regulates cystine starvation induced ferroptosis through malic enzyme 1 in pancreatic cancer cells. bioRxiv. 2023.doi: 10.1101/2023.09.15.557984. PubMed/NCBI

107 

Singh S, Maurya P, Rani S, Mishra N, Nisha R, Singh P and Saraf SA: Development of doxorubicin hydrochloride-loaded whey protein nanoparticles and its surface modification with N-acetyl cysteine for triple-negative breast cancer. Drug Deliv Transl Res. 12:3047–3062. 2022. View Article : Google Scholar : PubMed/NCBI

108 

Hangauer MJ, Viswanathan VS, Ryan MJ, Bole D, Eaton JK, Matov A, Galeas J, Dhruv HD, Berens ME, Schreiber SL, et al: Drug-tolerant persister cancer cells are vulnerable to GPX4 inhibition. Nature. 551:247–250. 2017. View Article : Google Scholar : PubMed/NCBI

109 

Zhang Y, Swanda RV, Nie L, Liu X, Wang C, Lee H, Lei G, Mao C, Koppula P, Cheng W, et al: mTORC1 couples cyst(e)ine availability with GPX4 protein synthesis and ferroptosis regulation. Nat Commun. 12:15892021. View Article : Google Scholar : PubMed/NCBI

110 

Jiang L, Kon N, Li T, Wang SJ, Su T, Hibshoosh H, Baer R and Gu W: Ferroptosis as a p53-mediated activity during tumour suppression. Nature. 520:57–62. 2015. View Article : Google Scholar : PubMed/NCBI

111 

Dixon SJ, Patel DN, Welsch M, Skouta R, Lee ED, Hayano M, Thomas AG, Gleason CE, Tatonetti NP, Slusher BS and Stockwell BR: Pharmacological inhibition of cystine-glutamate exchange induces endoplasmic reticulum stress and ferroptosis. Elife. 3:e025232014. View Article : Google Scholar : PubMed/NCBI

112 

Lu B, Chen XB, Ying MD, He QJ, Cao J and Yang B: The role of ferroptosis in cancer development and treatment response. Front Pharmacol. 8:9922018. View Article : Google Scholar : PubMed/NCBI

113 

Lei M, Zhang YL, Huang FY, Chen HY, Chen MH, Wu RH, Dai SZ, He GS, Tan GH and Zheng WP: Gankyrin inhibits ferroptosis through the p53/SLC7A11/GPX4 axis in triple-negative breast cancer cells. Sci Rep. 13:219162023. View Article : Google Scholar : PubMed/NCBI

114 

Tajan M and Vousden KH: Dietary approaches to cancer therapy. Cancer Cell. 37:767–785. 2020. View Article : Google Scholar : PubMed/NCBI

115 

Liu H, Zhang W, Wang K, Wang X, Yin F, Li C, Wang C, Zhao B, Zhong C, Zhang J, et al: Methionine and cystine double deprivation stress suppresses glioma proliferation via inducing ROS/autophagy. Toxicol Lett. 232:349–355. 2015. View Article : Google Scholar : PubMed/NCBI

116 

Knott SRV, Wagenblast E, Khan S, Kim SY, Soto M, Wagner M, Turgeon MO, Fish L, Erard N, Gable AL, et al: Asparagine bioavailability governs metastasis in a model of breast cancer. Nature. 554:378–381. 2018. View Article : Google Scholar : PubMed/NCBI

117 

Jimenez-Alonso JJ and Lopez-Lazaro M: Dietary manipulation of amino acids for cancer therapy. Nutrients. 15:28792023. View Article : Google Scholar : PubMed/NCBI

118 

Zhang T, Bauer C, Newman AC, Uribe AH, Athineos D, Blyth K and Maddocks ODK: Polyamine pathway activity promotes cysteine essentiality in cancer cells. Nat Metab. 2:1062–1076. 2020. View Article : Google Scholar : PubMed/NCBI

119 

Srivastava MK, Sinha P, Clements VK, Rodriguez P and Ostrand-Rosenberg S: Myeloid-derived suppressor cells inhibit T-cell activation by depleting cystine and cysteine. Cancer Res. 70:68–77. 2010. View Article : Google Scholar : PubMed/NCBI

120 

Wang W, Green M, Choi JE, Gijón M, Kennedy PD, Johnson JK, Liao P, Lang X, Kryczek I, Sell A, et al: CD8+ T cells regulate tumour ferroptosis during cancer immunotherapy. Nature. 569:270–274. 2019. View Article : Google Scholar : PubMed/NCBI

121 

Cramer SL, Saha A, Liu J, Tadi S, Tiziani S, Yan W, Triplett K, Lamb C, Alters SE, Rowlinson S, et al: Systemic depletion of L-cyst(e)ine with cyst(e)inase increases reactive oxygen species and suppresses tumor growth. Nat Med. 23:120–127. 2017. View Article : Google Scholar : PubMed/NCBI

122 

Alothaim T, Charbonneau M and Tang X: HDAC6 inhibitors sensitize non-mesenchymal triple-negative breast cancer cells to cysteine deprivation. Sci Rep. 11:109562021. View Article : Google Scholar : PubMed/NCBI

123 

Espinoza IKC, Park CH, Vander Steen T, Kleer CG, Wiley E, Rademaker A, Cuyàs E, Verdura S, Buxó M, Reynolds C, et al: Depletion of CCN1/CYR61 reduces triple-negative/basal-like breast cancer aggressiveness. Am J Cancer Res. 12:839–851. 2022.PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Xiao W and Xu C: Cystine/cysteine metabolism regulates the progression and response to treatment of triple‑negative breast cancer (Review). Oncol Lett 28: 521, 2024.
APA
Xiao, W., & Xu, C. (2024). Cystine/cysteine metabolism regulates the progression and response to treatment of triple‑negative breast cancer (Review). Oncology Letters, 28, 521. https://doi.org/10.3892/ol.2024.14654
MLA
Xiao, W., Xu, C."Cystine/cysteine metabolism regulates the progression and response to treatment of triple‑negative breast cancer (Review)". Oncology Letters 28.5 (2024): 521.
Chicago
Xiao, W., Xu, C."Cystine/cysteine metabolism regulates the progression and response to treatment of triple‑negative breast cancer (Review)". Oncology Letters 28, no. 5 (2024): 521. https://doi.org/10.3892/ol.2024.14654
Copy and paste a formatted citation
x
Spandidos Publications style
Xiao W and Xu C: Cystine/cysteine metabolism regulates the progression and response to treatment of triple‑negative breast cancer (Review). Oncol Lett 28: 521, 2024.
APA
Xiao, W., & Xu, C. (2024). Cystine/cysteine metabolism regulates the progression and response to treatment of triple‑negative breast cancer (Review). Oncology Letters, 28, 521. https://doi.org/10.3892/ol.2024.14654
MLA
Xiao, W., Xu, C."Cystine/cysteine metabolism regulates the progression and response to treatment of triple‑negative breast cancer (Review)". Oncology Letters 28.5 (2024): 521.
Chicago
Xiao, W., Xu, C."Cystine/cysteine metabolism regulates the progression and response to treatment of triple‑negative breast cancer (Review)". Oncology Letters 28, no. 5 (2024): 521. https://doi.org/10.3892/ol.2024.14654
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team