The emerging role of hypoxia-inducible factor-2 involved in chemo/radioresistance in solid tumors

Cancer Treatment Reviews

Volumn 41, Issue 7, 2015, Pages 623-633

  Zhao, Jiuda ^a,b,c   Du, Feng ^a,b   Luo, Yang ^a,b   Shen, Guoshuang ^c   Zheng, Fangchao ^c   Xu, Binghe ^a,b  

^a CANCER HOSPITAL   (China)

^b PEKING UNION MEDICAL COLLEGE   (China)

^c QINGHAI UNIVERSITY   (China)

Author keywords

Cancer; Chemo radioresistance; HIF 2; Hypoxia

Indexed keywords

ANTINEOPLASTIC AGENT; HYPOXIA INDUCIBLE FACTOR 1ALPHA; HYPOXIA INDUCIBLE FACTOR 2 INHIBITOR; HYPOXIA INDUCIBLE FACTOR 2ALPHA; UNCLASSIFIED DRUG; BASIC HELIX LOOP HELIX TRANSCRIPTION FACTOR; ENDOTHELIAL PAS DOMAIN-CONTAINING PROTEIN 1;

APOPTOSIS; CANCER CHEMOTHERAPY; CANCER GENETICS; CANCER RADIOTHERAPY; CANCER RESISTANCE; CARCINOGENESIS; CELL PROLIFERATION; CHEMORADIOTHERAPY; CHEMOSENSITIVITY; DNA DAMAGE; DNA REPAIR; DRUG EFFICACY; DRUG TRANSPORT; HUMAN; HYPOXIA; MULTIDRUG RESISTANCE; NONHUMAN; PROTEIN FUNCTION; RADIOSENSITIVITY; REGULATORY MECHANISM; REVIEW; SOLID TUMOR; TRANSCRIPTION REGULATION; TUMOR HYPOXIA; CELL HYPOXIA; NEOPLASMS; PATHOLOGY; PHYSIOLOGY;

BASIC HELIX-LOOP-HELIX TRANSCRIPTION FACTORS; CELL HYPOXIA; HUMANS; NEOPLASMS;

EID: 84937635983     PISSN: 03057372     EISSN: 15321967     Source Type: Journal    
DOI: 10.1016/j.ctrv.2015.05.004     Document Type: Review

References (129)

1. Gray L.H., Conger A.D., Ebert M., Honrsey S., Scott O.C. The concentration of oxygen dissolved in tissues at the time of irradiation as a factor in radiotherapy. Br J Radio 1953, 26:638.
2. Gordan J.D., Simon M.C. Hypoxia-inducible factors: central regulators of the tumor phenotype. Curr Opin Genet Dev 2007, 17:71-77.
3. Roizin-Towle L., Hall E.J. Studies with bleomycin and misonidazole on aerated and hypoxic cells. Br J Cancer 1978, 37:254-260.
4. Teicher B.A. Hypoxia and drug-resistance. Cancer Metast Rev 1994, 13:139-168.
5. Tian H., McKnight S.L., Russell D.W. Endothelial PAS domain protein 1 (EPAS1), a transcription factor selectively expressed in endothelial cells. Genes Dev 1997, 11:72-82.
6. Ema M., Taya S., Yokotani N., Sogawa K., Matsuda Y., Fujii-Kuriyama Y. A novel bHLH-PAS factor with close sequence similarity to hypoxia-inducible factor 1alpha regulates the VEGF expression and is potentially involved in lung and vascular development. Proc Natl Acad Sci USA 1997, 94:4273-4278.
7. Flamme I., Fröhlich T., von Reutern M., Kappel A., Damert A., Risau W. HRF, a putative basic helixloop-helix-PAS-domain transcription factor is closely related to hypoxia-inducible factor-1 alpha and developmentally expressed in blood vessels. Mech Dev 1997, 63:51-60.
8. Hogenesch J.B., Chan W.K., Jackiw V.H., Brown R.C., Gu Y.Z., Pray-Grant M., et al. Characterization of a subset of the basic-helix-loop-helix-PAS superfamily that interacts with components of the dioxin signaling pathway. J Biol Chem 1997, 272:8581-8593.
9. Mahon P.C., Semenza G.L. FIH-1: a novel protein that interacts with HIF-1alpha and VHL to mediate repression of HIF-1 transcriptional activity. Genes Dev 2001, 15:2675-2686.
10. Jaakkola P., Mole D.R., Tian Y.M., Wilson M.I., Gielbert J., Gaskell S.J., et al. Targeting of HIF-alpha to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation. Science 2001, 292:468-472.
11. Maxwell P.H., Pugh C.W., Ratcliffe P.J. Activation of the HIF pathway in cancer. Curr Opin Genet Dev 2001, 11:293-299.
12. Gatti L., Zunino F. Overview of tumor cell chemoresistance mechanisms. Methods Mol Med 2005, 111:127-148.
13. Gottesman M.M. Mechanisms of cancer drug resistance. Annu Rev Med 2002, 53:615-627.
14. Vaupel P., Thews O., Hoeckel M. Treatment resistance of solid tumours: role of hypoxia and anemia. Med Oncol 2001, 18:243-259.
15. Dachs G.U., Tozer G.M. Hypoxia modulated gene expression: angiogenesis, metastasis and therapeutic exploitation. Eur J Cancer 2000, 36:1649-1660.
16. Bertout J.A., Patel S.A., Simon M.C. The impact of O2 availability on human cancer. Nat Rev Cancer 2008, 8:967-975.
17. Wilson W.R., Hay M.P. Targeting hypoxia in cancer therapy. Nat Rev Cancer 2011, 11:393-410.
18. Denko N.C., Fontana L.A., Hudson K.M., Sutphin P.D., Raychaudhuri S., Altman R., et al. Investigating hypoxic tumor physiology through gene expression patterns. Oncogene 2003, 22:5907-5914.
19. Iyer N.V., Kotch L.E., Agani F., Leung S.W., Laughner E., Wenger R.H., et al. Cellular and developmental control of O2 homeostasis by hypoxia-inducible factor 1 alpha. Genes Dev 1998, 12:149-162.
20. Lofstedt T., Fredlund E., Holmquist-Mengelbier L., Pietras A., Ovenberger M., Poellinger L., et al. Hypoxia inducible factor-2alpha in cancer. Cell Cycle 2007, 6:919-926.
21. Chintala S., Najrana T., Toth K., Cao S., Durrani F.A., Pili R., et al. Prolyl hydroxylase 2 dependent and Von-Hippel-Lindau independent degradation of Hypoxia-inducible factor 1 and 2 alpha by selenium in clear cell renal cell carcinoma leads to tumor growth inhibition. BMC Cancer 2012, 12:293.
22. Gudas L.J., Fu L., Minton D.R., Mongan N.P., Nanus D.M. The role of HIF1α in renal cell carcinoma tumorigenesis. J Mol Med (Berl) 2014, 92:825-836.
23. Fu L., Wang G., Shevchuk M.M., Nanus D.M., Gudas L.J. Generation of a mouse model of von Hippel-Lindau kidney disease leading to renal cancers by expression of a constitutively active mutant of HIF1α. Cancer Res 2011, 71:6848-6856.
24. Holmquist-Mengelbier L., Fredlund E., Löfstedt T., Noguera R., Navarro S., Nilsson H., et al. Recruitment of HIF-1alpha and HIF-2alpha to common target genes is differentially regulated in neuroblastoma: HIF-2alpha promotes an aggressive phenotype. Cancer Cell 2006, 10:413-423.
25. Koh M.Y., Lemos R., Liu X., Powis G. The hypoxia-associated factor switches cells from HIF-1{alpha}- to HIF-2{alpha}-dependent signaling promoting stem cell characteristics, aggressive tumor growth and invasion. Cancer Res 2011, 71:4015-4027.
26. Camps C., Buffa F.M., Colella S., Moore J., Sotiriou C., Sheldon H., et al. Hsa-miR-210 is induced by hypoxia and is an independent prognostic factor in breast. Cancer. Clin Cancer Res 2008, 14:1340-1348.
27. Bruning U., Cerone L., Neufeld Z., Fitzpatrick S.F., Cheong A., Scholz C.C., et al. MicroRNA-155 promotes resolution of hypoxia-inducible factor 1α activity during prolonged hypoxia. Mol Cell Biol 2011, 31:4087-4096.
28. Yang W., Sun T., Cao J., Liu F., Tian Y., Zhu W. Downregulation of miR-210 expression inhibits proliferation, induces apoptosis and enhances radiosensitivity in hypoxic human hepatoma cells in vitro. Exp Cell Res 2012, 318:944-954.
29. Mathew L.K., Skuli N., Mucaj V., Lee S.S., Zinn P.O., Sathyan P., et al. MiR-218 opposes a critical RTK-HIF pathway in mesenchymal glioblastoma. Proc Natl Acad Sci USA 2014, 111:291-296.
30. Keith B., Johnson R.S., Simon M.C. HIF1α and HIF2α: sibling rivalry in hypoxic tumor growth and progression. Nat Rev Cancer 2012, 12:9-22.
31. Koh M.Y., Powis G. Passing the baton: the HIF switch. Trends Biochem Sci 2012, 37:364-372.
32. Loboda A., Jozkowicz A., Dulak J. HIF-1 versus HIF-2 is one more important than the other?. Vascul Pharmacol 2012, 56:245-251.
33. Raval R.R., Lau K.W., Tran M.G., Sowter H.M., Mandriota S.J., Li J.L., et al. Contrasting properties of hypoxia-inducible factor 1 (HIF-1) and HIF-2 in von Hippel-Lindau-associated renal cell carcinoma. Mol Cell Biol 2005, 25:5675-5686.
34. Carroll V.A., Ashcroft M. Role of hypoxia-inducible factor (HIF)-1alpha versus HIF-2alpha in the regulation of HIF target genes in response to hypoxia, insulin-like growth factor-I, or loss of von Hippel-Lindau function: implications for targeting the HIF pathway. Cancer Res 2006, 66:6264-6270.
35. Wang Y., Li Z., Zhang H., Jin H., Sun L., Dong H., et al. HIF-1α and HIF-2α correlate with migration and invasion in gastric cancer. Cancer Biol Ther 2010, 15:376-382.
36. Bertout J.A., Majmundar A.J., Gordan J.D., Lam J.C., Ditsworth D., Keith B., et al. HIF2alpha inhibition promotes p53 pathway activity, tumor cell death, and radiation responses. Proc Natl Acad Sci USA 2009, 106:14391-14396.
37. Talks K.L., Turley H., Gatter K.C., Maxwell P.H., Pugh C.W., Ratcliffe P.J., et 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 2000, 157:411-421.
38. Imtiyaz H.Z., Williams E.P., Hickey M.M., Patel S.A., Durham A.C., Yuan L.J., et al. Hypoxia-inducible factor 2α regulates macrophage function in mouse models of acute and tumor inflammation. J Clin Invest 2010, 120:2699-2714.
39. Xu Z., Zhao L., Zhu L.Y., He M., Zheng L., Wu Y. MicroRNA-17, 20a regulates the proangiogenic function of tumor-associated macrophages via targeting hypoxia-inducible factor 2α. PLoS ONE 2013, 8:e77890.
40. Rankin E.B., Giaccia A.J. The role of hypoxia-inducible factors in tumorigenesis. Cell Death Differ 2008, 15:678-685.
41. Patel S., Simon M.C. Biology of hypoxia-inducible factor-2α in development and disease. Cell Death Differ 2008, 15:628-634.
42. Rohwer N., Cramer T. Hypoxia-mediated drug resistance: novel insights on the functional interaction of HIFs and cell death pathways. Drug Resist Updat 2011, 14:191-201.
43. Lu C.W., Lin S.C., Chien C.W., Lee C.T., Lin B.W., Lee J.C., et al. Overexpression of pyruvate dehydrogenase kinase 3 increases drug resistance and early recurrence in colon cancer. Am J Pathol 2011, 179:1405-1414.
44. Plati J., Bucur O., Khosravi-Far R. Apoptotic cell signaling in cancer progression and therapy. Integr Biol (Camb) 2011, 3:279-296.
45. Maddika S., Ande S.R., Panigrahi S., Paranjothy T., Weglarczyk K., Zuse A., et al. Cell survival, cell death and cell cycle pathways are interconnected: implications for cancer therapy. Drug Resist Updat 2007, 10:13-29.
46. He C., Sun X.P., Qiao H., Jiang X., Wang D., Jin X., et al. Downregulating hypoxia-inducible factor-2α improves the efficacy of doxorubicin in the treatment of hepatocellular carcinoma. Cancer Sci 2012, 103:528-534.
47. Stoleriu M.G., Steger V., Mustafi M., Schneider W., Wendel H.P., Walker T., et al. A new strategy in the treatment of chemoresistant lung adenocarcinoma via sirna specific silencing of SRF, E2F1, survivin, HIF and STAT 3. Eur J Cardiothorac Surg 2014, 46:877-886.
48. Selvarajah J., Nathawat K., Moumen A., Ashcroft M., Carroll V.A. Chemotherapy-mediated p53-dependent DNA damage response in clear cell renal cell carcinoma: role of the mTORC1/2 and hypoxia-inducible factor pathways. Cell Death Dis 2013, 4:e865.
49. Carson B., Carbonaro1 M., O'Brate A., Giannakakou P. Loss of microtubule-dependent HIF regulation in renal cell carcinoma. Cancer Res 2010, 70(Suppl 1). (abstract 4079).
50. Jin F., Ji H., Jia C., Brockmeier U., Hermann D.M., Metzen E., et al. Synergistic antitumor effects of endostar in combination with oxaliplatin via inhibition of HIF and CXCR4 in the colorectal cell line SW1116. PLoS ONE 2012, 7:e47161.
51. Liu S., Kumar S.M., Martin J.S., Yang R., Xu X. Snail1 mediates hypoxia-induced melanoma progression. Am J Pathol 2011, 179:3020-3031.
52. Bordji K., Grandval A., Cunha-Alves L., Lechapt-Zalcman E., Bernaudin M. Class III beta-tubulin is a target gene of HIF-2alpha in glioblastoma cells exposed to hypoxia. Eur J Cancer 2014, 50(Suppl. 5):S41. (abstract 182).
53. Koukourakis M.I., Giatromanolaki A., Sivridis E., Simopoulos C., Turley H., Talks K., et al. Hypoxia-inducible factor (HIF1A and HIF2A), angiogenesis, and chemoradiotherapy outcome of squamous cell head-and-neck cancer. Int J Radiat Oncol Biol Phys 2002, 53:1192.
54. Haar C.P., Hebbar P., Wallace G.C., Das A., Vandergrift W.A., Smith J.A., et al. Drug resistance in glioblastoma: a mini review. Neurochem Res 2012, 37:1192-1200.
55. Sermeus A., Rebucci M., Fransolet M., Flamant L., Desmet D., Delaive E., et al. Differential effect of hypoxia on etoposide-induced DNA damage response and p53 regulation in different cell types. J Cell Physiol 2013, 228:2365-2376.
56. Gordan J.D., Bertout J.A., Hu C.J., Diehl J.A., Simon M.C. HIF-2alpha promotes hypoxic cell proliferation by enhancing c-myc transcriptional activity. Cancer Cell 2007, 11:335-347.
57. Biswas S., Troy H., Leek R., Chung Y.L., Li J.L., Raval R.R., et al. Effects of HIF-1alpha and HIF2alpha on growth and metabolism of clear-cell renal cell carcinoma 786-0 xenografts. J Oncol 2010, 2010:757908.
58. Scully R., Xie A. Double strand break repair functions of histone H2AX. Mutat Res 2013, 750:5-14.
59. Wirthner R., Wrann S., Balamurugan K., Wenger R.H., Stiehl D.P. Impaired DNA double-strand break repair contributes to chemoresistance in HIF-1 α-deficient mouse embryonic fibroblasts. Carcinogenesis 2008, 29:2306-2316.
60. Wrann S., Kaufmann M.R., Wirthner R., Stieh D.P., Wenger R.H. HIF mediated and DNA damage independent histone H2AX phosphorylation in chronic hypoxia. Biol Chem 2013, 394:519-528.
61. Cuvillier O., Ader I., Bouquerel P., Brizuela L., Gstalder C., Malavaud B. Hypoxia, therapeutic resistance, and sphingosine 1-phosphate. Adv Cancer Res 2012, 117:117-141.
62. Nakanishi T., Ross D.D. Breast cancer resistance protein (BCRP/ABCG2): its role in multidrug resistance and regulation of its gene expression. Chin J Cancer 2012, 31:73-99.
63. Zhang J.H., Feng Y.G., Gao G.P., Tao Y.Y., Zhang X.Q., Zhang H.M., et al. Effects of CagA+ Helicobacter pylori infection on expression of HIF-2α and ABCG2 in human gastric cancer cell line SGC7901 under normoxia and hypoxia conditions. World Chin J Digestol 2013, 21:293-299.
64. Zhang X.Q., Feng Y.G., Wu M.Y., Zhu Y., Bai H.X., Wang X.Y. Effect of 5-Fu on the ratio of SP cells and expression of HIF-2α and ABCG2 in human gastric cancer cell line SGC7901 under hypoxia. World Chin J Digestol 2012, 20:1813-1818.
65. Zhang X.Q., Zhang H.M., Sun X.E., Yuan Z.J., Feng Y.G. Inhibitory effects and mechanism of 5-fluorouracil combined with celecoxib on human gastric cancer xenografts in nude mice. Exp Ther Med 2015, 9:105-111.
66. Gordan J.D., Thompson C.B., Simon M.C. HIF and c-Myc: sibling rivals for control of cancer cell metabolism and proliferation. Cancer Cell 2007, 12:108-113.
67. Chun S.Y., Johnson C., Washburn J.G., Cruz-Correa M.R., Dang D.T., Dang L.H. Oncogenic KRAS modulates mitochondrial metabolism in human colon cancer cells by inducing HIF-1α and HIF-2α target genes. Mol Cancer 2010, 9:293.
68. Cleven A.H., Wouters B.G., Schutte B., Spiertz A.J., van Engeland M., de Bruïne A.P. Poorer outcome in stromal HIF-2 alpha- and CA9-positive colorectal adenocarcinomas is associated with wild-type TP53 but not with BNIP3 promoter hypermethylation or apoptosis. Br J Cancer 2008, 99:727-733.
69. AI-Hajj M., Wicha M.S., Benito-Hernandez A., Morrison S.J., Clarke M.F. Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci USA 2003, 100:3983-3988.
70. Singh S.K., Hawkins C., Clarke I.D., Squire J.A., Bayani J., Hide T., et al. Identification of human brain tumour initiating cells. Nature 2004, 432:396-401.
71. Salnikov A.V., Liu L., Platen M., Gladkich J., Salnikova O., Ryschich E., et al. Hypoxia induces EMT in low and highly aggressive pancreatic tumor cells but only cells with cancer stem cell characteristics acquire pronounced migratory potential. PLoS ONE 2012, 7:e46391.
72. Kolenda J., Jensen S.S., Aaberg-Jessen C., Christensen K., Andersen C., Brünner N., et al. Effects of hypoxia on expression of a panel of stem cell and chemoresistance markers in glioblastoma-derived spheroids. J Neurooncol 2011, 103:43-58.
73. So J.Y., Suh N. Targeting cancer stem cells in solid tumors by vitamin D. J Steroid Biochem Mol Biol 2015, 148:79-85.
74. Bandopadhyay G., Grabowska A.M., Coyle B., Watson S.A. Functional role of CD133 in glioblastoma multiforme. Cancer Res 2010, 70(Suppl. 1):8. (abstract 4306).
75. Santoyo-Ramos P., Likhatcheva M., García-Zepeda E.A., Castañ eda-Patlán M.C., Robles-Flores M. Hypoxia-inducible factors modulate the stemness and malignancy of colon cancer cells by playing opposite roles in canonical wnt signaling. PLoS ONE 2014, 9:e112580.
76. William W.N., Glisson B.S. Novel strategies for the treatment of small-cell lung carcinoma. Nat Rev Clin Oncol 2011, 8:611-619.
77. Llovet J.M., Ricci S., Mazzaferro V., Hilgard P., Gane E., Blanc J.F., et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 2008, 24:378-390.
78. Villanueva A., Llovet J.M. Second-line therapies in hepatocellular carcinoma: emergence of resistance to sorafenib. Clin Cancer Res 2012, 18:1824-1826.
79. Zhao D., Zhai B., He C., Tan G., Jiang X., Pan S., et al. Upregulation of HIF-2α induced by sorafenib contributes to the resistance by activating the TGF-α/EGFR pathway in hepatocellular carcinoma cells. Cell Signal 2014, 26:1030-1039.
80. Ma L., Li G., Zhu H., Dong X., Zhao D., Jiang X., et al. 2-Methoxyestradiol synergizes with sorafenib to suppress hepatocellular carcinoma by simultaneously dysregulating hypoxia-inducible factor-1 and -2. Cancer Lett 2014, 355:96-105.
81. Zhu B., Lin S.S., Liu P.F., Li Y.F., Gao H.Y., Su Z.Y., et al. Desumoylation of hypoxia inducible factor (hif)-2a by senp1 is involved in HPPCn-enhanced sorafenib resistance under hypoxia in hepatocellular carcinoma. J Hepatol 2014, 60(Suppl. 1):1. (abstract 51).
82. Zhao C.X., Luo C.L., Wu X.H. Hypoxia promotes 786-O cells invasiveness and resistance to sorafenib via HIF-2α/COX-2. Med Oncol 2015, 32:419.
83. Burkitt K., Chun S.Y., Dang D.T., Dang L.H. Targeting both HIF-1 and HIF-2 in human colon cancer cells improves tumor response to sunitinib treatment. Mol Cancer Ther 2009, 8:1148-1156.
84. Yasuda H. Solid tumor physiology and hypoxia-induced chemo/radio-resistance: novel strategy for cancer therapy: nitric oxide donor as a therapeutic enhancer. Nitric Oxide 2008, 19:205-216.
85. Harada H., Kizaka-Kondoh S., Li G., Itasaka S., Shibuya K., Inoue M., et al. Significance of HIF-1-active cells in angiogenesis and radioresistance. Oncogene 2007, 26:7508-7516.
86. Bhatt R.S., Landis D.M., Zimmer M., et al. Hypoxia-inducible factor-2alpha: effect on radiation sensitivity and differential regulation by an mTOR inhibitor. BJU Int 2008, 102:358-363.
87. Zhou J., Wu K., Gao D., Zhu G., Wu D., Wang X., et al. Reciprocal regulation of hypoxia-inducible factor 2α and GLI1 expression associated with the radioresistance of renal cell carcinoma. Int J Radiat Oncol Biol Phys 2014, 90:942-951.
88. Ströfer M., Jelkmann W., Metzen E., Brockmeier U., Dunst J., Depping R. Stabilisation and knockdown of HIF-two distinct ways comparably important in radiotherapy. Cell Physiol Biochem 2011, 28:805-812.
89. Pietras A., Katz A.M., Ekström E.J., Wee B., Halliday J.J., Pitter K.L., et al. Osteopontin-CD44 signaling in the glioma perivascular niche enhances cancer stem cell phenotypes and promotes aggressive tumor growth. Cell Stem Cell 2014, 14:357-369.
90. Brown L.M., Cowen R.L., Debray C., Eustace A., Erler J.T., Sheppard F.C., et al. Reversing hypoxic cell chemoresistance in vitro using genetic and small molecule approaches targeting hypoxia inducible factor-1. Mol Pharmacol 2006, 69:411-418.
91. Sasabe E., Zhou X., Li D., Oku N., Yamamoto T., Osaki T. The involvementof hypoxia-inducible factor-1alpha in the susceptibility to gamma-rays and chemotherapeutic drugs of oral squamous cell carcinoma cells. Int J Cancer 2007, 120:268-277.
92. Wen Y.A., Stevens P.D., Gasser M.L., Andrei R., Gao T. Downregulation of PHLPP expression contributes to hypoxia-induced resistance to chemotherapy in colon cancer cells. Mol Cell Biol 2013, 33:4594-4605.
93. Cho K., Shin H.W., Kim Y.I., Cho C.H., Chun Y.S., Kim T.Y., et al. Mad1 mediates hypoxia-induced doxorubicin resistance in colon cancer cells by inhibiting mitochondrial function. Free Radic Biol Med 2013, 60:201-210.
94. Grandori C., Cowley S.M., James L.P., Eisenman R.N. The Myc/Max/Mad network and the transcriptional control of cell behavior. Annu Rev Cell Dev Biol 2000, 16:653-699.
95. Florczyk U., Czauderna S., Stachurska A., Tertil M., Nowak W., Kozakowska M. Opposite effects of HIF-1α and HIF-2α on the regulation of IL-8 expression in endothelial cells. Free Radic Biol Med 2011, 51:1882-1892.
96. Imamura T., Kikuchi H., Herraiz M.T., Park D.Y., Mizukami Y., Mino-Kenduson M., et al. HIF-1α and HIF-2α have divergent roles in colon cancer. Int J Cancer 2009, 124:763-771.
97. Carew J.S., Esquivel J.A., Espitia C.M., Schultes C.M., Mülbaier M., Lewis J.D., et al. ELR510444 inhibits tumor growth and angiogenesis by abrogating HIF activity and disrupting microtubules in renal cell carcinoma. PLoS ONE 2012, 7:e31120.
98. Mabjeesh N.J., Escuin D., LaVallee T.M., Pribluda V.S., Swartz G.M., Johnson M.S., et al. 2ME2 inhibits tumor growth and angiogenesis by disrupting microtubules and dysregulating HIF. Cancer Cell 2003, 3:363-375.
99. Puppo M., Battaglia F., Ottaviano C., Delfino S., Ribatti D., Varesio L., et al. Topotecan inhibits vascular endothelial growth factor production and angiogenic activity induced by hypoxia in human neuroblastoma by targeting hypoxia-inducible factor-1alpha and -2alpha. Mol Cancer Ther 2008, 7:1974-1984.
100. Roberts A.M., Watson I.R., Evans A.J., Foster D.A., Irwin M.S., Ohh M. Suppression of hypoxia-inducible factor 2alpha restores p53 activity via Hdm2 and reverses chemoresistance of renal carcinoma cells. Cancer Res 2009, 69:9056-9064.
101. Zimmer M., Lamb J., Ebert B.L., Lynch M., Neil C., Schmidt E., et al. The connectivity map links iron regulatory protein-1-mediated inhibition of hypoxia-inducible factor-2a translation to the anti-inflammatory 15-deoxy-delta12,14-prostaglandin J2. Cancer Res 2010, 70:3071-3079.
102. Bae W.J., Shin M.R., Kang S.K., Jun Z., Kim J.Y., Lee S.C., et al. HIF-2 inhibition supresses inflammatory responses and osteoclastic differentiation in human periodontal ligament cells. J Cell Biochem 2015, doi: 101002/jcb25078.
103. Nilsson M.B., Zage P.E., Zeng L., Xu L., Cascone T., Wu H.K., et al. Multiple receptor tyrosine kinases regulate HIF-1alpha and HIF-2alpha in normoxia and hypoxia in neuroblastoma: implications for antiangiogenic mechanisms of multikinase inhibitors. Oncogene 2010, 29:2938-2949.
104. Clinical trial registration: URL:https://clinicaltrials.gov/ct2/home,%20NCT02293980.
105. Lee S.Y., Chung S.M. Neovastat (AE-941) inhibits the airway inflammation via VEGF and HIF-2 alpha suppression. Vascul Pharmacol 2007, 47(5-6):313-318.
106. Ye F., Che Y., McMillen E., Gorski J., Brodman D., Saw D., et al. The effect of Scutellaria baicalensis on the signaling network in hepatocellular carcinoma cells. Nutr Cancer 2009, 61:530-537.
107. Burrows N., Babur M., Resch J., Ridsdale S., Mejin M., Rowling E.J., et al. GDC-0941 inhibits metastatic characteristics of thyroid carcinomas by targeting both the phosphoinositide-3 kinase (PI3K) and hypoxia-inducible factor-1alpha (HIF-1alpha) pathways. J Clin Endocrinol Metab 2011, 96. E1934-43.
108. Sato A., Virgona N., Ando A., Ota M., Yano T. A redox-silent analogue of tocotrienol inhibits cobalt(II) chloride-induced VEGF expression via Yes signaling in mesothelioma cells. Biol Pharm Bull 2014, 37:865-870.
109. Ellinghaus P., Heisler I., Unterschemmann K., Haerter M., Beck H., Greschat S., et al. BAY 87-2243, a highly potent and selective inhibitor of hypoxia-induced gene activation has antitumor activities by inhibition of mitochondrial complex I. Cancer Med 2013, 2:611-624.
110. Nozawa-Suzuki N., Nagasawa H., Ohnishi K., Morishige K. The inhibitory effect of hypoxic cytotoxin on the expansion of cancer stem cells in ovarian cancer. Biochem Biophys Res Commun 2015, 457:706-711.
111. McKee T.C., Rabe D., Bokesch H.R., Grkovic T., Whitson E.L., Diyabalanage T., et al. Inhibition of hypoxia inducible factor-2 transcription: isolation of active modulators from marine sponges. J Nat Prod 2012, 75:1632-1636.
112. Härter M., Thierauch K.H., Boyer S., Bhargava A., Ellinghaus P., Beck H., et al. Inhibition of hypoxia-induced gene transcription by substituted pyrazolyl oxadiazoles: initial lead generation and structure-activity relationships. Chem Med Chem 2014, 9:61-66.
113. Grkovic T., Whitson E.L., Rabe D.C., Gardella R.S., Bottaro D.P., Linehan W.M., et al. Identification and evaluation of soft coral diterpenes as inhibitors of HIF-2α induced gene expression. Bioorg Med Chem Lett 2011, 21:2113-2115.
114. Lee K., Zhang H., Qian D.Z., Rey S., Liu J.O., Semenza G.L. Acriflavine inhibits HIF-1 dimerization, tumor growth, and vascularization. Proc Natl Acad Sci USA 2009, 106:17910-17915.
115. Scheuermann T.H., Li Q., Ma H.W., Key J., Zhang L., Chen R., et al. Allosteric inhibition of hypoxia inducible factor-2 with small molecules. Nat Chem Biol 2013, 9:271-276.
116. Scheuermann T.H., Tomchick D.R., Machius M., Guo Y., Bruick R.K., Gardner K.H. Artificial ligand binding within the HIF2alpha PAS-B domain of the HIF2 transcription factor. Proc Natl Acad Sci USA 2009, 106:450-455.
117. Zhao J., Du F., Shen G., Zheng F., Xu B. The role of hypoxia-inducible factor-2 in digestive system cancers. Cell Death Dis 2015, 6:e1600.
118. Kong H.S., Lee S., Beebe K., Scroggins B., Gupta G., Lee M.J., et al. Emetine promotes von Hippel-Lindau-independent degradation of hypoxia-inducible factor-2alpha in clear cell renal carcinoma. Mol Pharmacol 2010, 78:1072-1078.
119. Guan Y., Reddy K.R., Zhu Q., Li Y., Lee K., Weerasinghe P., et al. G-rich oligonucleotides inhibit HIF-1alpha and HIF-2alpha and block tumor growth. Mol Ther 2010, 18:188-197.
120. Joshi S., Singh A.R., Durden D.L. Pan-PI-3 kinase inhibitor SF1126 shows antitumor and antiangiogenic activity in renal cell carcinoma Cancer. Chemother Pharmacol 2015, 75:595-608.
121. David J.M., Owens T.A., Inge L.J., Bremner R.M., Rajasekaran A.K. Gramicidin A blocks tumor growth and angiogenesis through inhibition of hypoxia-inducible factor in renal cell carcinoma. Mol Cancer Ther 2014, 13:788-799.
122. Neelam S., Brooks M.M., Cammarata P.R. Lenticular cytoprotection. Part 1: the role of hypoxia inducible factors-1alpha and -2alpha and vascular endothelial growth factor in lens epithelial cell survival in hypoxia. Mol Vis 2013, 19:1-15.
123. Fath D.M., Kong X., Liang D., Lin Z., Chou A., Jiang Y., et al. Histone deacetylase inhibitors repress the transactivation potential of hypoxia-inducible factors independently of direct acetylation of HIF-alpha. J Biol Chem 2006, 281:13612-13619.
124. Sosman J.A., Puzanov I., Atkins M.B. Opportunities and obstacles to combination targeted therapy in renal cell cancer. Clin Cancer Res 2007, 13:764s-769s.
125. Li S.H., Shin D.H., Chun Y.S., Lee M.K., Kim M.S., Park J.W. A novel mode of action of YC-1 in HIF inhibition: stimulation of FIH-dependent p300 dissociation from HIF-1{alpha}. Mol Cancer Ther 2008, 7:3729-3738.
126. Gonzalez-Flores A., Aguilar-Quesada R., Siles E., Pozo S., Rodríguez-Lara M.I., López-Jiménez L., et al. Interaction between PARP-1 and HIF-2alpha in the hypoxic response. Oncogene 2014, 33:891-898.
127. Bokesch H.R., Gardella R.S., Rabe D.C., Bottaro D.P., Linehan W.M., McMahon J.B., et al. A new hypoxia inducible factor-2 inhibitory pyrrolinone alkaloid from roots and stems of Piper sarmentosum. Chem Pharm Bull (Tokyo) 2011, 59:1178-1179.
128. Xie M., He C.S., Huang J.K., Lin Q.Z. Phase II study of pazopanib as second-line treatment after sunitinib in patients with metastatic renal cell carcinoma: a Southern China urology cancer consortium trial. Eur J Cancer 2015, 51:595-603.
129. Makino Y., Kanopka A., Wilson W.J., Tanaka H., Poellinger L. Inhibitory PAS domain protein (IPAS) is a hypoxia-inducible splicing variant of the hypoxia-inducible factor-3alpha locus. J Biol Chem 2002, 277:32405-32408.