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 Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1021-335X Online ISSN: 1791-2431
Journal Cover
January-2020 Volume 43 Issue 1

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
January-2020 Volume 43 Issue 1

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

Hypoxia‑inducible factors in hepatocellular carcinoma (Review)

  • Authors:
    • Yang Guo
    • Zunqiang Xiao
    • Liu Yang
    • Yuling Gao
    • Qiaojuan Zhu
    • Linjun Hu
    • Dongsheng Huang
    • Qiuran Xu
  • View Affiliations / Copyright

    Affiliations: Graduate Department, BengBu Medical College, Bengbu, Anhui 233030, P.R. China, The Second Clinical Medical Department, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310014, P.R. China, The Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Zhejiang Provincial People's Hospital (People's Hospital of Hangzhou Medical College), Hangzhou, Zhejiang 310014, P.R. China, Department of Genetics, Shaoxing Women and Children Hospital, Shaoxin, Zhejiang 312030, P.R. China, Medical Department, Qingdao University, Qingdao, Shandong 266071, P.R. China
    Copyright: © Guo et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 3-15
    |
    Published online on: November 1, 2019
       https://doi.org/10.3892/or.2019.7397
  • 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

Maintenance of an appropriate oxygen concentration is essential for the function of the liver. However, in many pathological conditions, and particularly in the tumor microenvironment, cells and tissues are frequently in a hypoxic state. In the presence of hypoxia, the cells adapt to the low oxygen levels through the hypoxia‑inducible factor (HIF) pathway. Overgrowth of tumor cells restricts the diffusion of oxygen in tumors, leading to insufficient blood supply and the creation of a hypoxic microenvironment, and, as a consequence, activation of the expression of HIFs. HIFs possess a wide range of target genes, which function to control a variety of signaling pathways; thus, HIFs modulate cellular metabolism, immune escape, angiogenesis, metastasis, extracellular matrix remodeling, cancer stem cells and other properties of the tumor. Given their crucial role in the occurrence and development of tumors, HIFs are expected to become new targets of precise treatment of hepatocellular carcinoma.
View Figures

Figure 1

Figure 2

Figure 3

View References

1 

Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, Jemal A, Yu XQ and He J: Cancer statistics in China, 2015. Ca Cancer J Clin. 66:115–132. 2016. View Article : Google Scholar : PubMed/NCBI

2 

Mckeown SR: Defining normoxia, physoxia and hypoxia in tumours-implications for treatment response. Br J Radiol. 87:201306762014. View Article : Google Scholar : PubMed/NCBI

3 

Cui CP, Wong CC, Kai AK, Ho DW, Lau EY, Tsui YM, Chan LK, Cheung TT, Chok KS, Chan ACY, et al: SENP1 promotes hypoxia-induced cancer stemness by HIF-1α deSUMOylation and SENP1/HIF-1α positive feedback loop. Gut. 66:2149–2159. 2017. View Article : Google Scholar : PubMed/NCBI

4 

Wang J, Ma Y, Jiang H, Zhu H, Liu L, Sun B, Pan S, Krissansen GW and Sun X: Overexpression of von Hippel-Lindau protein synergizes with doxorubicin to suppress hepatocellular carcinoma in mice. J Hepatol. 55:359–368. 2011. View Article : Google Scholar : PubMed/NCBI

5 

Blagosklonny MV: Hypoxia-inducible factor: Achilles' heel of antiangiogenic cancer therapy (Review). Int J Oncol. 19:257–262. 2001.PubMed/NCBI

6 

Dengler VL, Galbraith MD and Espinosa JM: Transcriptional regulation by hypoxia inducible factors. Crit Rev Biochem Mol Biol. 49:1–15. 2014. View Article : Google Scholar : PubMed/NCBI

7 

Hu CJ, Sataur A, Wang L, Chen H and Simon MC: The N-terminal Transactivation domain confers target gene specificity of hypoxia-inducible factors HIF-1alpha and HIF-2alpha. Mol Biol Cell. 18:4528–4542. 2007. View Article : Google Scholar : PubMed/NCBI

8 

Ohh M, Park CW, Ivan M, Hoffman MA, Kim TY, Huang LE, Pavletich N, Chau V and Kaelin WG: Ubiquitination of hypoxia-inducible factor requires direct binding to the beta-domain of the von Hippel-Lindau protein. Nat Cell Biol. 2:423–427. 2000. View Article : Google Scholar : PubMed/NCBI

9 

Maxwell PH, Wiesener MS, Chang GW, Clifford SC, Vaux EC, Cockman ME, Wykoff CC, Pugh CW, Maher ER and Ratcliffe PJ: The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis. Nature. 399:271–275. 1999. View Article : Google Scholar : PubMed/NCBI

10 

Ivan M, Kondo K, Yang H, Kim W, Valiando J, Ohh M, Salic A, Asara JM, Lane WS and Kaelin WG Jr: HIFalpha targeted for VHL-mediated destruction by proline hydroxylation: Implications for O2 sensing. Science. 292:464–468. 2001. View Article : Google Scholar : PubMed/NCBI

11 

Garvalov BK and Acker T: Implications of oxygen homeostasis for tumor biology and treatment. 903:169–185. 2016.PubMed/NCBI

12 

Benita Y, Kikuchi H, Smith AD, Zhang MQ, Chung DC and Xavier RJ: An integrative genomics approach identifies Hypoxia Inducible Factor-1 (HIF-1)-target genes that form the core response to hypoxia. Nucleic Acids Res. 37:4587–4602. 2009. View Article : Google Scholar : PubMed/NCBI

13 

Salminen A, Kauppinen A and Kaarniranta K: 2-Oxoglutarate- dependent dioxygenases are sensors of energy metabolism, oxygen availability, and iron homeostasis: Potential role in the regulation of aging process. Cell Mol Life Sci. 72:3897–3914. 2015. View Article : Google Scholar : PubMed/NCBI

14 

Briggs KJ, Koivunen P, Cao S, Backus KM, Olenchock BA, Patel H, Zhang Q, Signoretti S, Gerfen GJ, Richardson AL, et al: Paracrine Induction of HIF by glutamate in breast cancer: EglN1 senses cysteine. Cell. 166:126–139. 2016. View Article : Google Scholar : PubMed/NCBI

15 

Lau CK, Yang ZF, Ho DW, Ng MN, Yeoh GC, Poon RT and Fan ST: An AKT/hypoxia-inducible factor-1alpha/platelet-derived growth factor-BB autocrine loop mediates hypoxia-induced chemoresistance in liver cancer cells and tumorigenic hepatic progenitor cells. Clin Cancer Res. 15:3462–3471. 2009. View Article : Google Scholar : PubMed/NCBI

16 

Akeno N, Robins J, Zhang M, Czyzyk-Krzeska MF and Clemens TL: Induction of vascular endothelial growth factor by IGF-I in osteoblast-like cells is mediated by the PI3K signaling pathway through the hypoxia-inducible factor-2alpha. Endocrinology. 143:420–425. 2002. View Article : Google Scholar : PubMed/NCBI

17 

Fukuda R, Hirota K, Fan F, Jung YD, Ellis LM and Semenza GL: Insulin-like growth factor 1 induces hypoxia-inducible factor 1-mediated vascular endothelial growth factor expression, which is dependent on MAP kinase and phosphatidylinositol 3-kinase signaling in colon cancer cells. J Biol Chem. 277:38205–38211. 2002. View Article : Google Scholar : PubMed/NCBI

18 

Biswas S, Mukherjee R, Tapryal N, Singh AK and Mukhopadhyay CK: Insulin regulates hypoxia-inducible factor-1α transcription by reactive oxygen species sensitive activation of Sp1 in 3T3-L1 preadipocyte. PLoS One. 8:e621282013. View Article : Google Scholar : PubMed/NCBI

19 

Laughner E, Taghavi P, Chiles K, Mahon PC and Semenza GL: HER2 (neu) signaling increases the rate of hypoxia-inducible factor 1alpha (HIF-1alpha) synthesis: Novel mechanism for HIF-1-mediated vascular endothelial growth factor expression. Mol Cell Biol. 21:3995–4004. 2001. View Article : Google Scholar : PubMed/NCBI

20 

Nayak BK, Feliers D, Sudarshan S, Friedrichs WE, Day RT, New DD, Fitzgerald JP, Eid A, Denapoli T, Parekh DJ, et al: Stabilization of HIF-2α through redox regulation of mTORC2 activation and initiation of mRNA translation. Oncogene. 32:3147–3155. 2013. View Article : Google Scholar : PubMed/NCBI

21 

Liu LZ, Hu XW, Xia C, He J, Zhou Q, Shi X, Fang J and Jiang BH: Reactive oxygen species regulate epidermal growth factor-induced vascular endothelial growth factor and hypoxia-inducible factor-1alpha expression through activation of AKT and P70S6K1 in human ovarian cancer cells. Free Radic Biol Med. 41:1521–1533. 2006. View Article : Google Scholar : PubMed/NCBI

22 

Jiang BH, Jiang G, Zheng JZ, Lu Z, Hunter T and Vogt PK: Phosphatidylinositol 3-kinase signaling controls levels of hypoxia-inducible factor 1. Cell Growth Differ. 12:363–369. 2001.PubMed/NCBI

23 

Lim JH, Lee YM, Chun YS, Chen J, Kim JE and Park JW: Sirtuin 1 modulates cellular responses to hypoxia by deacetylating hypoxia-inducible factor 1alpha. Mol Cell. 38:864–878. 2010. View Article : Google Scholar : PubMed/NCBI

24 

Liu X, Chen S, Tu J, Cai W and Xu Q: HSP90 inhibits apoptosis and promotes growth by regulating HIF-1α abundance in hepatocellular carcinoma. Int J Mol Med. 37:825–835. 2016. View Article : Google Scholar : PubMed/NCBI

25 

van Hagen M, Overmeer RM, Abolvardi SS and Vertegaal AC: RNF4 and VHL regulate the proteasomal degradation of SUMO-conjugated Hypoxia-Inducible Factor-2alpha. Nucleic Acids Res. 38:1922–1931. 2010. View Article : Google Scholar : PubMed/NCBI

26 

Duan C: Hypoxia-inducible factor 3 biology: Complexities and emerging themes. Am J Physiol Cell Physiol. 310:C260–C269. 2016. View Article : Google Scholar : PubMed/NCBI

27 

Makino Y, Kanopka A, Wilson WJ, Tanaka H and Poellinger L: Inhibitory PAS domain protein (IPAS) is a hypoxia-inducible splicing variant of the hypoxia-inducible factor-3alpha locus. J Biol Chem. 277:32405–32408. 2002. View Article : Google Scholar : PubMed/NCBI

28 

Maynard MA, Qi H, Chung J, Lee EH, Kondo Y, Hara S, Conaway RC, Conaway JW and Ohh M: Multiple splice variants of the human HIF-3 alpha locus are targets of the von Hippel-Lindau E3 ubiquitin ligase complex. J Biol Chem. 278:11032–11040. 2003. View Article : Google Scholar : PubMed/NCBI

29 

Heikkilä M, Pasanen A, Kivirikko KI and Myllyharju J: Roles of the human hypoxia-inducible factor (HIF)-3α variants in the hypoxia response. Cell Mol Life Sci. 68:3885–3901. 2011. View Article : Google Scholar : PubMed/NCBI

30 

Chen C and Lou T: Hypoxia inducible factors in hepatocellular carcinoma. Oncotarget. 8:46691–46703. 2017.PubMed/NCBI

31 

Mucaj V, Shay JE and Simon MC: Effects of hypoxia and HIFs on cancer metabolism. Int J Hematol. 95:464–470. 2012. View Article : Google Scholar : PubMed/NCBI

32 

Warburg O, Wind F and Negelein E: The metabolism of tumors in the body. J Gen Physiol. 8:519–530. 1927. View Article : Google Scholar : PubMed/NCBI

33 

Alfarouk KO, Verduzco D, Rauch C, Muddathir AK, Adil HH, Elhassan GO, Ibrahim ME, David Polo Orozco J, Cardone RA, Reshkin SJ and Harguindey S: Glycolysis, tumor metabolism, cancer growth and dissemination. A new pH-based etiopathogenic perspective and therapeutic approach to an old cancer question. Oncoscience. 1:777–802. 2014. View Article : Google Scholar : PubMed/NCBI

34 

Liberti MV and Locasale JW: The warburg effect: How does it benefit cancer cells? Trends Biochem Sci. 41:211–218. 2016. View Article : Google Scholar : PubMed/NCBI

35 

Denko NC: Hypoxia, HIF1 and glucose metabolism in the solid tumour. Nat Rev Cancer. 8:705–713. 2008. View Article : Google Scholar : PubMed/NCBI

36 

Semenza GL: Regulation of cancer cell metabolism by hypoxia-inducible factor 1. Semin Cancer Biol. 19:12–16. 2009. View Article : Google Scholar : PubMed/NCBI

37 

Semenza GL: HIF-1: Upstream and downstream of cancer metabolism. Curr Opin Genet Dev. 20:51–56. 2010. View Article : Google Scholar : PubMed/NCBI

38 

Ke Q and Costa M: Hypoxia-Inducible Factor-1 (HIF-1). Mol Pharmacol. 70:1469–1480. 2006. View Article : Google Scholar : PubMed/NCBI

39 

Marín-Hernández A, Gallardo-Pérez JC, Ralph SJ, Rodríguez-Enríquez S and Moreno-Sánchez R: HIF-1alpha modulates energy metabolism in cancer cells by inducing over-expression of specific glycolytic isoforms. Mini Rev Med Chem. 9:1084–1091. 2009. View Article : Google Scholar : PubMed/NCBI

40 

Kim JW, Tchernyshyov I, Semenza GL and Dang CV: HIF-1-mediated expression of pyruvate dehydrogenase kinase: A metabolic switch required for cellular adaptation to hypoxia. Cell Metab. 3:177–185. 2006. View Article : Google Scholar : PubMed/NCBI

41 

Weidemann A and Johnson RS: Biology of HIF-1 alpha. Cell Death Differ. 15:621–627. 2008. View Article : Google Scholar : PubMed/NCBI

42 

Graziano F, Ruzzo A, Giacomini E, Ricciardi T, Aprile G, Loupakis F, Lorenzini P, Ongaro E, Zoratto F, Catalano V, et al: Glycolysis gene expression analysis and selective metabolic advantage in the clinical progression of colorectal cancer. Pharmacogenomics J. 17:258–264. 2017. View Article : Google Scholar : PubMed/NCBI

43 

Schito L and Semenza GL: Hypoxia-inducible factors: Master regulators of cancer progression. Trends Cancer. 2:758–770. 2016. View Article : Google Scholar : PubMed/NCBI

44 

Samanta D, Park Y, Ni X, Li H, Zahnow CA, Gabrielson E, Pan F and Semenza GL: Chemotherapy induces enrichment of CD47+/CD73+/PDL1+immune evasive triple-negative breast cancer cells. Proc Natl Acad Sci USA. 115:E1239–E1248. 2018. View Article : Google Scholar : PubMed/NCBI

45 

Terry S, Buart S and Chouaib S: Hypoxic stress-induced tumor and immune plasticity, suppression, and impact on tumor heterogeneity. Front Immunol. 8:16252017. View Article : Google Scholar : PubMed/NCBI

46 

Noman MZ, Janji B, Kaminska B, Moer KV, Pierson S, Przanowski P, Buart S, Berchem G, Romero P, Mami-Chouaib F and Chouaib S: Blocking hypoxia-induced autophagy in tumors restores cytotoxic t-cell activity and promotes regression. Autophagy. 71:5976–5986. 2012.

47 

Hatfield SM and Sitkovsky M: A2A adenosine receptor antagonists to weaken the hypoxia-HIF-1α driven immunosuppression and improve immunotherapies of cancer. Curr Opin Pharmacol. 29:90–96. 2016. View Article : Google Scholar : PubMed/NCBI

48 

Vinit K and Gabrilovich DI: Hypoxia-inducible factors in regulation of immune responses in tumour microenvironment. Immunology. 143:512–519. 2014. View Article : Google Scholar : PubMed/NCBI

49 

Fukuda K, Kobayashi A and Watabe K: The role of tumor- associated macrophage in tumor progression. Front Biosci. 4:787–798. 2012.

50 

Zhu XD, Zhang JB, Zhuang PY, Zhu HG, Zhang W, Xiong YQ, Wu WZ, Wang L, Tang ZY and Sun HC: High expression of macrophage colony-stimulating factor in peritumoral liver tissue is associated with poor survival after curative resection of hepatocellular carcinoma. J Clin Oncol. 26:2707–2716. 2008. View Article : Google Scholar : PubMed/NCBI

51 

Wu Q, Zhou W, Yin S, Zhou Y, Chen T, Qian J, Su R, Hong L, Lu H, Zhang F, et al: Blocking TREM-1 Tumor-associated macrophages induced by hypoxia reverses immunosuppression and anti-PD-L1 resistance in liver cancer. Hepatology. 70:198–214. 2019.PubMed/NCBI

52 

Zeisberger SM, Odermatt B, Marty C, Zehnder-Fjällman AH, Ballmer-Hofer K and Schwendener RA: Clodronate-liposome- mediated depletion of tumour-associated macrophages: A new and highly effective antiangiogenic therapy approach. Br J Cancer. 95:272–281. 2006. View Article : Google Scholar : PubMed/NCBI

53 

Kuang DM, Peng C, Zhao Q, Wu Y, Chen MS and Zheng L: Activated monocytes in peritumoral stroma of hepatocellular carcinoma promote expansion of memory T helper 17 cells. Hepatology. 51:154–164. 2010. View Article : Google Scholar : PubMed/NCBI

54 

Jiang J, Wang GZ, Wang Y, Huang HZ, Li WT and Qu XD: Hypoxia-induced HMGB1 expression of HCC promotes tumor invasiveness and metastasis via regulating macrophage-derived IL-6. Exp Cell Res. 367:81–88. 2018. View Article : Google Scholar : PubMed/NCBI

55 

Ye LY, Chen W, Bai XL, Xu XY, Zhang Q, Xia XF, Sun X, Li GG, Hu QD, Fu QH and Liang TB: Hypoxia-induced epithelial-to-mesenchymal transition in hepatocellular carcinoma induces an immunosuppressive tumor microenvironment to promote metastasis. Cancer Res. 76:818–830. 2016. View Article : Google Scholar : PubMed/NCBI

56 

Payne SJ and Louise J: Influence of the tumor microenvironment on angiogenesis. Future Oncol. 7:395–408. 2011. View Article : Google Scholar : PubMed/NCBI

57 

Branco-Price C, Zhang N, Schnelle M, Evans C, Katschinski DM, Liao D, Ellies L and Johnson RS: Endothelial cell HIF-1α and HIF-2α differentially regulate metastatic success. Cancer Cell. 21:52–65. 2012. View Article : Google Scholar : PubMed/NCBI

58 

De Francesco EM, Lappano R, Santolla MF, Marsico S, Caruso A and Maggiolini M: HIF-1α/GPER signaling mediates the expression of VEGF induced by hypoxia in breast cancer associated fibroblasts (CAFs). Breast Cancer Res. 15:R642013. View Article : Google Scholar : PubMed/NCBI

59 

Ahluwalia A and Tarnawski AS: Critical role of hypoxia sensor-HIF-1α in VEGF gene activation. Implications for angiogenesis and tissue injury healing. Curr Med Chem. 19:90–97. 2012. View Article : Google Scholar : PubMed/NCBI

60 

Lee K, Zhang H, Qian DZ, Rey S, Liu JO and Semenza GL: Acriflavine inhibits HIF-1 dimerization, tumor growth, and vascularization. Proc Natl Acad Sci USA. 106:17910–17915. 2009. View Article : Google Scholar : PubMed/NCBI

61 

Wang W, Xu GL, Jia WD, Wang ZH, Li JS, Ma JL, Ge YS, Xie SX and Yu JH: Expression and correlation of hypoxia-inducible factor-1alpha, vascular endothelial growth factor and microvessel density in experimental rat hepatocarcinogenesis. J Int Med Res. 37:417–425. 2009. View Article : Google Scholar : PubMed/NCBI

62 

Liu LP, Ho RL, Chen GG and Lai PB: Sorafenib inhibits hypoxia-inducible factor-1α synthesis: Implications for antiangiogenic activity in hepatocellular carcinoma. Clin Cancer Res. 18:5662–5671. 2012. View Article : Google Scholar : PubMed/NCBI

63 

Semenza GL: Defining the role of hypoxia-inducible factor 1 in cancer biology and therapeutics. Oncogene. 29:625–634. 2010. View Article : Google Scholar : PubMed/NCBI

64 

Li H, Ge C, Zhao F, Yan M, Hu C, Jia D, Tian H, Zhu M, Chen T, Jiang G, et al: Hypoxia-inducible factor 1 alpha-activated angiopoietin-like protein 4 contributes to tumor metastasis via vascular cell adhesion molecule-1/integrin β1 signaling in human hepatocellular carcinoma. Hepatology. 54:910–919. 2011. View Article : Google Scholar : PubMed/NCBI

65 

Tian H, McKnight SL and Russell DW: Endothelial PAS domain protein 1 (EPAS1), a transcription factor selectively expressed in endothelial cells. Genes Dev. 11:72–82. 1997. View Article : Google Scholar : PubMed/NCBI

66 

Talks KL, Turley H, Gatter KC, Maxwell PH, Pugh CW, Ratcliffe PJ and Harris AL: The expression and distribution of the hypoxia-inducible factors HIF-1alpha and HIF-2alpha in normal human tissues, cancers, and tumor-associated macrophages. Am J Pathol. 157:411–421. 2000. View Article : Google Scholar : PubMed/NCBI

67 

Wiesener MS, Jürgensen JS, Rosenberger C, Scholze CK, Hörstrup JH, Warnecke C, Mandriota S, Bechmann I, Frei UA, Pugh CW, et al: Widespread hypoxia-inducible expression of HIF-2alpha in distinct cell populations of different organs. FASEB J. 17:271–273. 2003. View Article : Google Scholar : PubMed/NCBI

68 

Zhang T, Niu X, Liao L, Cho EA and Yang H: The Contributions of HIF-Target Genes to Tumor Growth in RCC. PLoS One. 8:e805442013. View Article : Google Scholar : PubMed/NCBI

69 

Feng N, Chen H, Fu S, Bian Z, Lin X, Yang L, Gao Y, Fang J and Ge Z: HIF-1α and HIF-2α induced angiogenesis in gastrointestinal vascular malformation and reversed by thalidomide. Sci Rep. 6:272802016. View Article : Google Scholar : PubMed/NCBI

70 

Aprelikova O, Wood M, Tackett S, Chandramouli GV and Barrett JC: Role of ETS transcription factors in the hypoxia-inducible factor-2 target gene selection. Cancer Res. 66:5641–5647. 2006. View Article : Google Scholar : PubMed/NCBI

71 

Evans AJ, Russell RC, Roche O, Burry TN, Fish JE, Chow VW, Kim WY, Saravanan A, Maynard MA, Gervais ML, et al: VHL promotes E2 box-dependent E-cadherin transcription by HIF-mediated regulation of SIP1 and snail. Mol Cell Biol. 27:157–169. 2007. View Article : Google Scholar : PubMed/NCBI

72 

Zhang L, Huang G, Li X, Zhang Y, Jiang Y, Shen J, Liu J, Wang Q, Zhu J, Feng X, et al: Hypoxia induces epithelial-mesenchymal transition via activation of SNAI1 by hypoxia-inducible factor-1α in hepatocellular carcinoma. Bmc Cancer. 13:1082013. View Article : Google Scholar : PubMed/NCBI

73 

Willis BC, Liebler JM, Luby-Phelps K, Nicholson AG, Crandall ED, du Bois RM and Borok Z: Induction of epithelial-mesenchymal transition in alveolar epithelial cells by transforming growth factor-beta1: Potential role in idiopathic pulmonary fibrosis. Am J Pathol. 166:1321–1332. 2005. View Article : Google Scholar : PubMed/NCBI

74 

Copple BL: Hypoxia stimulates hepatocyte epithelial to mesenchymal transition by hypoxia-inducible factor and transforming growth factor-beta-dependent mechanisms. Liver Int. 30:669–682. 2010. View Article : Google Scholar : PubMed/NCBI

75 

Wang XH, Liu MN, Sun X, Xu CH, Liu J, Chen J, Xu RL and Li BX: TGF-β1 pathway affects the protein expression of many signaling pathways, markers of liver cancer stem cells, cytokeratins, and TERT in liver cancer HepG2 cells. Tumor Biol. 37:3675–3681. 2016. View Article : Google Scholar

76 

Erler JT and Giaccia AJ: Lysyl oxidase mediates hypoxic control of metastasis. Cancer Res. 66:10238–10241. 2006. View Article : Google Scholar : PubMed/NCBI

77 

Sahlgren C, Gustafsson MV, Jin S, Poellinger L and Lendahl U: Notch signaling mediates hypoxia-induced tumor cell migration and invasion. Proc Natl Acad Sci USA. 105:6392–6397. 2008. View Article : Google Scholar : PubMed/NCBI

78 

Gustafsson MV, Zheng X, Pereira T, Gradin K, Jin S, Lundkvist J, Ruas JL, Poellinger L, Lendahl U and Bondesson M: Hypoxia requires notch signaling to maintain the undifferentiated cell state. Dev Cell. 9:617–628. 2005. View Article : Google Scholar : PubMed/NCBI

79 

D'Ignazio L, Batie M and Rocha S: Hypoxia and inflammation in cancer, focus on HIF and NF-κB. Biomedicines. 5:E212017. View Article : Google Scholar : PubMed/NCBI

80 

Fitzpatrick SF, Tambuwala MM, Bruning U, Schaible B, Scholz CC, Byrne A, O'Connor A, Gallagher WM, Lenihan CR, Garvey JF, et al: An intact canonical NF-κB pathway is required for inflammatory gene expression in response to hypoxia. J Immunol. 186:1091–1096. 2011. View Article : Google Scholar : PubMed/NCBI

81 

Taylor CT and Cummins EP: The role of NF-kappaB in hypoxia-induced gene expression. Ann N Y Acad Sci. 1177:178–184. 2010. View Article : Google Scholar

82 

Zhang L, Liu H, Mu X, Cui J and Peng Z: Dysregulation of Fra1 expression by Wnt/β-catenin signalling promotes glioma aggressiveness through epithelial-mesenchymal transition. Biosci Rep. 37:BSR201606432017. View Article : Google Scholar : PubMed/NCBI

83 

Zhang Q, Bai X, Chen W, Ma T, Hu Q, Liang C, Xie S, Chen C, Hu L, Xu S and Liang T: Wnt/β-catenin signaling enhances hypoxia-induced epithelial-mesenchymal transition in hepatocellular carcinoma via crosstalk with hif-1α signaling. Carcinogenesis. 34:962–973. 2013. View Article : Google Scholar : PubMed/NCBI

84 

Xu W, Zhou W, Cheng M, Wang J, Liu Z, He S, Luo X, Huang W, Chen T, Yan W and Xiao J: Hypoxia activates Wnt/β-catenin signaling by regulating the expression of BCL9 in human hepatocellular carcinoma. Sci Rep. 7:404462017. View Article : Google Scholar : PubMed/NCBI

85 

Dou C, Zhou Z, Xu Q, Liu Z, Zeng Y, Wang Y, Li Q, Wang L, Yang W, Liu Q and Tu K: Hypoxia-induced TUFT1 promotes the growth and metastasis of hepatocellular carcinoma by activating the Ca2+/PI3K/AKT pathway. Oncogene. 38:1239–1255. 2019. View Article : Google Scholar : PubMed/NCBI

86 

Liu Z, Tu K, Wang Y, Yao B, Li Q, Wang L, Dou C, Liu Q and Zheng X: Hypoxia accelerates aggressiveness of hepatocellular carcinoma cells involving oxidative stress, epithelial-mesenchymal transition and non-canonical hedgehog signaling. Cell Physiol Biochem. 44:1856–1868. 2017. View Article : Google Scholar : PubMed/NCBI

87 

An WG, Kanekal M, Simon MC, Maltepe E, Blagosklonny MV and Neckers LM: Stabilization of wild-type p53 by hypoxia-inducible factor 1alpha. Nature. 392:405–408. 1998. View Article : Google Scholar : PubMed/NCBI

88 

Hansson LO, Friedler A, Freund S, Rüdiger S and Fersht AR: Two sequence motifs from HIF-1alpha bind to the DNA-binding site of p53. Proc Natl Acad Sci USA. 99:10305–10309. 2002. View Article : Google Scholar : PubMed/NCBI

89 

Amelio I, Inoue S, Markert EK, Levine AJ, Knight RA, Mak TW and Melino G: TAp73 opposes tumor angiogenesis by promoting hypoxia-inducible factor 1α degradation. Proc Natl Acad Sci USA. 112:226–231. 2015. View Article : Google Scholar : PubMed/NCBI

90 

Liu Z, Wang J, Guo C and Fan X: microRNA-21 mediates epithelial-mesenchymal transition of human hepatocytes via PTEN/AKT pathway. Biomed Pharmacother. 69:24–28. 2015. View Article : Google Scholar : PubMed/NCBI

91 

Chang RM, Xu JF, Fang F, Yang H and Yang LY: MicroRNA-130b promotes proliferation and EMT-induced metastasis via PTEN/p-AKT/HIF-1α signaling. Tumor Biol. 37:10609–10619. 2016. View Article : Google Scholar

92 

Liu Z, Wang Y, Dou C, Xu M, Sun L, Wang L, Yao B, Li Q, Yang W, Tu K and Liu Q: Hypoxia-induced up-regulation of VASP promotes invasiveness and metastasis of hepatocellular carcinoma. Theranostics. 8:4649–4663. 2018. View Article : Google Scholar : PubMed/NCBI

93 

Li B, He L, Zuo D, He W, Wang Y, Zhang Y, Liu W and Yuan Y: Mutual Regulation of MiR-199a-5p and HIF-1α modulates the warburg effect in hepatocellular carcinoma. J Cancer. 8:940–949. 2017. View Article : Google Scholar : PubMed/NCBI

94 

Jia YY, Zhao JY, Li BL, Gao K, Song Y, Liu MY, Yang XJ, Xue Y, Wen AD and Shi L: miR-592/WSB1/HIF-1α axis inhibits glycolytic metabolism to decrease hepatocellular carcinoma growth. Oncotarget. 7:35257–35269. 2016. View Article : Google Scholar : PubMed/NCBI

95 

Chen Z, Zuo X, Zhang Y, Han G, Zhang L, Wu J and Wang X: MiR-3662 suppresses hepatocellular carcinoma growth through inhibition of HIF-1α-mediated Warburg effect. Cell Death Dis. 9:5492018. View Article : Google Scholar : PubMed/NCBI

96 

Guo XF, Wang AY and Liu J: HIFs-MiR-33a-Twsit1 axis can regulate invasiveness of hepatocellular cancer cells. Eur Rev Med Pharmacol Sci. 20:3011–3016. 2016.PubMed/NCBI

97 

Chai ZT, Kong J, Zhu XD, Zhang YY, Lu L, Zhou JM, Wang LR, Zhang KZ, Zhang QB, Ao JY, et al: MicroRNA-26a inhibits angiogenesis by down-regulating VEGFA through the PIK3C2α/AKT/HIF-1α pathway in hepatocellular carcinoma. PLoS One. 8:e779572013. View Article : Google Scholar : PubMed/NCBI

98 

Lin J, Cao S, Wang Y, Hu Y, Liu H, Li J, Chen J, Li P, Liu J, Wang Q and Zheng L: Long non-coding RNA UBE2CP3 enhances HCC cell secretion of VEGFA and promotes angiogenesis by activating ERK1/2/HIF-1α/VEGFA signalling in hepatocellular carcinoma. J Exp Clin Cancer Res. 37:1132018. View Article : Google Scholar : PubMed/NCBI

99 

Wang TH, Yu CC, Lin YS, Chen TC, Yeh CT, Liang KH, Shieh TM, Chen CY and Hsueh C: Long noncoding RNA CPS1-IT1 suppresses the metastasis of hepatocellular carcinoma by regulating HIF-1α activity and inhibiting epithelial-mesenchymal transition. Oncotarget. 7:43588–43603. 2016.PubMed/NCBI

100 

Bonnans C, Chou J and Werb Z: Remodelling the extracellular matrix in development and disease. Nat Rev Mol Cell Biol. 15:786–801. 2014. View Article : Google Scholar : PubMed/NCBI

101 

Rankin EB and Giaccia AJ: Hypoxic control of metastasis. Science. 352:175–180. 2016. View Article : Google Scholar : PubMed/NCBI

102 

Kai AK, Chan LK, Lo RC, Lee JM, Wong CC, Wong JC and Ng IO: Down-regulation of TIMP2 by HIF-1α/miR-210/HIF-3α regulatory feedback circuit enhances cancer metastasis in hepatocellular carcinoma. Hepatology. 64:473–487. 2016. View Article : Google Scholar : PubMed/NCBI

103 

Kalluri R: The biology and function of fibroblasts in cancer. Nat Rev Cancer. 16:582–598. 2016. View Article : Google Scholar : PubMed/NCBI

104 

Tse AP, Sze KM, Shea QT, Chiu EY, Tsang FH, Chiu DK, Zhang MS, Lee D, Xu IM, Chan CY, et al: Hepatitis transactivator protein X promotes extracellular matrix modification through HIF/LOX pathway in liver cancer. Oncogenesis. 7:442018. View Article : Google Scholar : PubMed/NCBI

105 

Cheng ZC and Sadek HA: Hypoxia and metabolic properties of hematopoietic stem cells. Antioxid Redox Signal. 20:1891–1901. 2014. View Article : Google Scholar : PubMed/NCBI

106 

Bao B, Azmi AS, Ali S, Ahmad A, Li Y, Banerjee S, Kong D and Sarkar FH: The biological kinship of hypoxia with CSC and EMT and their relationship with deregulated expression of miRNAs and tumor aggressiveness. Biochim Biophys Acta. 1826:272–296. 2012.PubMed/NCBI

107 

Lai FB, Liu WT, Jing YY, Yu GF, Han ZP, Yang X, Zeng JX, Zhang HJ, Shi RY, Li XY, et al: Lipopolysaccharide supports maintaining the stemness of CD133(+) hepatoma cells through activation of the NF-κB/HIF-1α pathway. Cancer Lett. 378:131–141. 2016. View Article : Google Scholar : PubMed/NCBI

108 

Jing L, Ruan Z, Sun H, Li Q, Han L, Huang L, Yu S, Wang Y, Guo H and Jiao M: Epithelial-mesenchymal transition induced cancer-stem-cell-like characteristics in hepatocellular carcinoma. J Cell Physiol. 234:18448–18458. 2019.PubMed/NCBI

109 

Cao Q, Lu W, Zhou T, Liu Y, Cai X, Zhu J and Cao P: Analgesic-antitumor peptide inhibits angiogenesis by suppressing AKT activation in hepatocellular carcinoma. Mol Cell Biochem. 455:119–125. 2019. View Article : Google Scholar : PubMed/NCBI

110 

Tan Y, Du B, Zhan Y, Wang K, Wang X, Chen B, Wei X and Xiao J: Antitumor effects of circ-EPHB4 in hepatocellular carcinoma via inhibition of HIF-1α. Mol Carcinog. 58:875–886. 2019. View Article : Google Scholar : PubMed/NCBI

111 

Qin Y, Liu HJ, Li M, Zhai DH, Tang YH, Yang L, Qiao KL, Yang JH, Zhong WL, Zhang Q, et al: Salidroside improves the hypoxic tumor microenvironment and reverses the drug resistance of platinum drugs via HIF-1α signaling pathway. EBioMedicine. 38:25–36. 2018. View Article : Google Scholar : PubMed/NCBI

112 

Lei HW, Cai J, Li CM, Yang F, Shi WQ, Shi WQ, Wang LP and Feng YY: Rapamycin combi with TAE on the growth, metastasis, and prognosis of hepatocellular carcinoma in rat models. Ann Hepatol. 17:645–654. 2018. View Article : Google Scholar : PubMed/NCBI

113 

Hua H, Zhu Y and Song YH: Ruscogenin suppressed the hepatocellular carcinoma metastasis via PI3K/AKT/mTOR signaling pathway. Biomed Pharmacother. 101:115–122. 2018. View Article : Google Scholar : PubMed/NCBI

114 

Liu P, Atkinson SJ, Akbareian SE, Zhou Z, Munsterberg A, Robinson SD and Bao Y: Sulforaphane exerts anti-angiogenesis effects against hepatocellular carcinoma through inhibition of STAT3/HIF-1α/VEGF signalling. Sci Rep. 7:126512017. View Article : Google Scholar : PubMed/NCBI

115 

Zhou QY, Tu CY, Shao CX, Wang WK, Zhu JD, Cai Y, Mao JY and Chen W: GC7 blocks epithelial-mesenchymal transition and reverses hypoxia-induced chemotherapy resistance in hepatocellular carcinoma cells. Am J Transl Res. 9:2608–2617. 2017.PubMed/NCBI

116 

Chow AK, Yau TC, Ng L, Chu AC, Law WL, Poon RT and Pang RW: A preclinical study on the combination therapy of everolimus and transarterial chemoembolization in hepatocellular carcinoma. Am J Cancer Res. 5:2376–2386. 2015.PubMed/NCBI

117 

Li C, Wu X, Zhang H, Yang G, Hao M, Sheng S, Sun Y, Long J, Hu C, Sun X, et al: A Huaier polysaccharide restrains hepatocellular carcinoma growth and metastasis by suppression angiogenesis. Int J Biol Macromol. 75:115–120. 2015. View Article : Google Scholar : PubMed/NCBI

118 

Wu J, Contratto M, Shanbhogue KP, Manji GA, O'Neil BH, Noonan A, Tudor R and Lee R: Evaluation of a locked nucleic acid form of antisense oligo targeting HIF-1α in advanced hepatocellular carcinoma. World J Clin Oncol. 10:149–160. 2019. View Article : Google Scholar : PubMed/NCBI

119 

Rapisarda A, Uranchimeg B, Sordet O, Pommier Y, Shoemaker RH and Melillo G: Topoisomerase I-mediated inhibition of hypoxia-inducible factor 1: Mechanism and therapeutic implications. Cancer Res. 64:1475–1482. 2004. View Article : Google Scholar : PubMed/NCBI

120 

Zhang C, Yang C, Feldman MJ, Wang H, Pang Y, Maggio DM, Zhu D, Nesvick CL, Dmitriev P, Bullova P, et al: Vorinostat suppresses hypoxia signaling by modulating nuclear translocation of hypoxia inducible factor 1 alpha. Oncotarget. 8:56110–56125. 2017.PubMed/NCBI

121 

Li YL, Zhang NY, Hu X, Chen JL, Rao MJ, Wu LW, Li QY, Zhang B, Yan W and Zhang C: Evodiamine induces apoptosis and promotes hepatocellular carcinoma cell death induced by vorinostat via downregulating HIF-1α under hypoxia. Biochem Biophys Res Commun. 498:481–486. 2018. View Article : Google Scholar : PubMed/NCBI

122 

Shao S, Duan W, Xu Q, Li X, Han L, Li W, Zhang D, Wang Z and Lei J: Curcumin suppresses hepatic stellate cell-induced hepatocarcinoma angiogenesis and invasion through downregulating CTGF. Oxid Med Cell Longev. 2019:81485102019. View Article : Google Scholar : PubMed/NCBI

123 

Xia Y, Choi HK and Lee K: Recent advances in hypoxia-inducible factor (HIF)-1 inhibitors. Eur J Med Chem. 49:24–40. 2012. View Article : Google Scholar : PubMed/NCBI

124 

Abu-Remaileh M, Khalaileh A, Pikarsky E and Aqeilan RI: Author Correction: WWOX controls hepatic HIF1α to suppress hepatocyte proliferation and neoplasia. Cell Death Dis. 9:11592018. View Article : Google Scholar : PubMed/NCBI

125 

Yang Q, Guo X and Yang L: Metformin enhances the effect of regorafenib and inhibits recurrence and metastasis of hepatic carcinoma after liver resection via regulating expression of hypoxia inducible factors 2α (HIF-2α) and 30 kDa HIV tat-interacting protein (TIP30). Med Sci Monit. 24:2225–2234. 2018. View Article : Google Scholar : PubMed/NCBI

126 

Wada H, Nagano H, Yamamoto H, Yang Y, Kondo M, Ota H, Nakamura M, Yoshioka S, Kato H, Damdinsuren B, et al: Expression pattern of angiogenic factors and prognosis after hepatic resection in hepatocellular carcinoma: Importance of angiopoietin-2 and hypoxia-induced factor-1 alpha. Liver Int. 26:414–423. 2006. View Article : Google Scholar : PubMed/NCBI

127 

Dai CX, Gao Q, Qiu SJ, Ju MJ, Cai MY, Xu YF, Zhou J, Zhang BH and Fan J: Hypoxia-inducible factor-1 alpha, in association with inflammation, angiogenesis and MYC, is a critical prognostic factor in patients with HCC after surgery. BMC Cancer. 9:4182009. View Article : Google Scholar : PubMed/NCBI

128 

Xia L, Mo P, Huang W, Zhang L, Wang Y, Zhu H, Tian D, Liu J, Chen Z, Zhang Y, et al: The TNF-α/ROS/HIF-1-induced upregulation of FoxMI expression promotes HCC proliferation and resistance to apoptosis. Carcinogenesis. 33:2250–2259. 2012. View Article : Google Scholar : PubMed/NCBI

129 

Xiang ZL, Zeng ZC, Fan J, Tang ZY, He J, Zeng HY and Chang JY: The expression of HIF-1α in primary hepatocellular carcinoma and its correlation with radiotherapy response and clinical outcome. Mol Biol Rep. 39:2021–2029. 2012. View Article : Google Scholar : PubMed/NCBI

130 

Zheng SS, Chen XH, Yin X and Zhang BH: Prognostic significance of HIF-1α expression in hepatocellular carcinoma: A meta-analysis. PLoS One. 8:e657532013. View Article : Google Scholar : PubMed/NCBI

131 

Wang B, Ding YM, Fan P, Wang B, Xu JH and Wang WX: Expression and significance of MMP2 and HIF-1α in hepatocellular carcinoma. Oncol Lett. 8:539–546. 2014. View Article : Google Scholar : PubMed/NCBI

132 

Cao S, Yang S, Wu C, Wang Y, Jiang J and Lu Z: Protein expression of hypoxia-inducible factor-1 alpha and hepatocellular carcinoma: A systematic review with meta-analysis. Clin Res Hepatol Gastroenterol. 38:598–603. 2014. View Article : Google Scholar : PubMed/NCBI

133 

Liu LP, Hu BG, Ye C, Ho RL, Chen GG and Lai PB: HBx mutants differentially affect the activation of hypoxia-inducible factor-1α in hepatocellular carcinoma. Br J Cancer. 110:1066–1073. 2014. View Article : Google Scholar : PubMed/NCBI

134 

Wang D, Zhang X, Lu Y, Wang X and Zhu L: Hypoxia inducible factor 1α in hepatocellular carcinoma with cirrhosis: Association with prognosis. Pathol Res Pract. 214:1987–1992. 2018. View Article : Google Scholar : PubMed/NCBI

135 

Bangoura G, Liu Z, Qian Q, Jiang C, Yang G and Jing S: Prognostic significance of HIF-2alpha/EPAS1 expression in hepatocellular carcinoma. World J Gastroenterol. 13:3176–3182. 2007. View Article : Google Scholar : PubMed/NCBI

136 

Sun HX, Xu Y, Yang XR, Wang WM, Bai H, Shi RY, Nayar SK, Devbhandari RP, He YZ, Zhu QF, et al: Hypoxia inducible factor 2 alpha inhibits hepatocellular carcinoma growth through the transcription factor dimerization partner 3/E2F transcription factor 1-dependent apoptotic pathway. Hepatology. 57:1088–1097. 2013. View Article : Google Scholar : PubMed/NCBI

137 

Yao Q, Lv Y, Pan T, Liu Y, Ma J and Xu G: Prognostic significance and clinicopathological features of hypoxic inducible factor-2alpha expression in hepatocellular carcinoma. Saudi Med J. 36:170–175. 2015. View Article : Google Scholar : PubMed/NCBI

138 

Yang SL, Liu LP, Niu L, Sun YF, Yang XR, Fan J, Ren JW, Chen GG and Lai PB: Downregulation and pro-apoptotic effect of hypoxia-inducible factor 2 alpha in hepatocellular carcinoma. Oncotarget. 7:34571–34581. 2016.PubMed/NCBI

139 

Jiang L, Liu QL, Liang QL, Zhang HJ, Ou WT and Yuan GL: Association of PHD3 and HIF2α gene expression with clinicopathological characteristics in human hepatocellular carcinoma. Oncol Lett. 15:545–551. 2018.PubMed/NCBI

140 

Liu P, Fang X, Song Y, Jiang JX, He QJ and Liu XJ: Expression of hypoxia-inducible factor 3α in hepatocellular carcinoma and its association with other hypoxia-inducible factors. Exp Ther Med. 11:2470–2476. 2016. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Guo Y, Xiao Z, Yang L, Gao Y, Zhu Q, Hu L, Huang D and Xu Q: Hypoxia‑inducible factors in hepatocellular carcinoma (Review). Oncol Rep 43: 3-15, 2020.
APA
Guo, Y., Xiao, Z., Yang, L., Gao, Y., Zhu, Q., Hu, L. ... Xu, Q. (2020). Hypoxia‑inducible factors in hepatocellular carcinoma (Review). Oncology Reports, 43, 3-15. https://doi.org/10.3892/or.2019.7397
MLA
Guo, Y., Xiao, Z., Yang, L., Gao, Y., Zhu, Q., Hu, L., Huang, D., Xu, Q."Hypoxia‑inducible factors in hepatocellular carcinoma (Review)". Oncology Reports 43.1 (2020): 3-15.
Chicago
Guo, Y., Xiao, Z., Yang, L., Gao, Y., Zhu, Q., Hu, L., Huang, D., Xu, Q."Hypoxia‑inducible factors in hepatocellular carcinoma (Review)". Oncology Reports 43, no. 1 (2020): 3-15. https://doi.org/10.3892/or.2019.7397
Copy and paste a formatted citation
x
Spandidos Publications style
Guo Y, Xiao Z, Yang L, Gao Y, Zhu Q, Hu L, Huang D and Xu Q: Hypoxia‑inducible factors in hepatocellular carcinoma (Review). Oncol Rep 43: 3-15, 2020.
APA
Guo, Y., Xiao, Z., Yang, L., Gao, Y., Zhu, Q., Hu, L. ... Xu, Q. (2020). Hypoxia‑inducible factors in hepatocellular carcinoma (Review). Oncology Reports, 43, 3-15. https://doi.org/10.3892/or.2019.7397
MLA
Guo, Y., Xiao, Z., Yang, L., Gao, Y., Zhu, Q., Hu, L., Huang, D., Xu, Q."Hypoxia‑inducible factors in hepatocellular carcinoma (Review)". Oncology Reports 43.1 (2020): 3-15.
Chicago
Guo, Y., Xiao, Z., Yang, L., Gao, Y., Zhu, Q., Hu, L., Huang, D., Xu, Q."Hypoxia‑inducible factors in hepatocellular carcinoma (Review)". Oncology Reports 43, no. 1 (2020): 3-15. https://doi.org/10.3892/or.2019.7397
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