• This record comes from PubMed

Hypoxia-inducible factors: master regulators of hypoxic tumor immune escape

. 2022 Jun 03 ; 15 (1) : 77. [epub] 20220603

Language English Country Great Britain, England Media electronic

Document type Journal Article, Review, Research Support, Non-U.S. Gov't

Grant support
31972741 Natural Science Foundation of Jilin Province
2016T90477 Postdoctoral Science Foundation of Jiangsu Province
759585 H2020 European Research Council

Links

PubMed 35659268
PubMed Central PMC9166526
DOI 10.1186/s13045-022-01292-6
PII: 10.1186/s13045-022-01292-6
Knihovny.cz E-resources

Hypoxia, a common feature of the tumor microenvironment in various types of cancers, weakens cytotoxic T cell function and causes recruitment of regulatory T cells, thereby reducing tumoral immunogenicity. Studies have demonstrated that hypoxia and hypoxia-inducible factors (HIFs) 1 and 2 alpha (HIF1A and HIF2A) are involved in tumor immune escape. Under hypoxia, activation of HIF1A induces a series of signaling events, including through programmed death receptor-1/programmed death ligand-1. Moreover, hypoxia triggers shedding of complex class I chain-associated molecules through nitric oxide signaling impairment to disrupt immune surveillance by natural killer cells. The HIF-1-galactose-3-O-sulfotransferase 1-sulfatide axis enhances tumor immune escape via increased tumor cell-platelet binding. HIF2A upregulates stem cell factor expression to recruit tumor-infiltrating mast cells and increase levels of cytokines interleukin-10 and transforming growth factor-β, resulting in an immunosuppressive tumor microenvironment. Additionally, HIF1A upregulates expression of tumor-associated long noncoding RNAs and suppresses immune cell function, enabling tumor immune escape. Overall, elucidating the underlying mechanisms by which HIFs promote evasion of tumor immune surveillance will allow for targeting HIF in tumor treatment. This review discusses the current knowledge of how hypoxia and HIFs facilitate tumor immune escape, with evidence to date implicating HIF1A as a molecular target in such immune escape. This review provides further insight into the mechanism of tumor immune escape, and strategies for tumor immunotherapy are suggested.

See more in PubMed

Galon J, Bruni D. Approaches to treat immune hot, altered and cold tumours with combination immunotherapies. Nat Rev Drug Discov. 2019;18(3):197–218. doi: 10.1038/s41573-018-0007-y. PubMed DOI

Lane AN, Higashi RM, Fan TW. Metabolic reprogramming in tumors: contributions of the tumor microenvironment. Genes Dis. 2020;7(2):185–198. doi: 10.1016/j.gendis.2019.10.007. PubMed DOI PMC

Binnewies M, Roberts EW, Kersten K, Chan V, Fearon DF, Merad M, et al. Understanding the tumor immune microenvironment (TIME) for effective therapy. Nat Med. 2018;24(5):541–550. doi: 10.1038/s41591-018-0014-x. PubMed DOI PMC

Bose S, Panda AK, Mukherjee S, Sa G. Curcumin and tumor immune-editing: resurrecting the immune system. Cell Div. 2015;10:1–13. doi: 10.1186/s13008-015-0012-z. PubMed DOI PMC

Lei X, Lei Y, Li JK, Du WX, Li RG, Yang J, et al. Immune cells within the tumor microenvironment: biological functions and roles in cancer immunotherapy. Cancer Lett. 2020;470:126–133. doi: 10.1016/j.canlet.2019.11.009. PubMed DOI

Wu Q, Wu W, Franca TCC, Jacevic V, Wang X, Kuca K. Immune evasion, a potential mechanism of trichothecenes: new insights into negative immune regulations. Int J Mol Sci. 2018;19(11):3307. doi: 10.3390/ijms19113307. PubMed DOI PMC

Wu Q, Wu W, Fu B, Shi L, Wang X, Kuca K. JNK signaling in cancer cell survival. Med Res Rev. 2019;39(6):2082–2104. doi: 10.1002/med.21574. PubMed DOI

Jiang XJ, Wang J, Deng XY, Xiong F, Ge JS, Xiang B, et al. Role of the tumor microenvironment in PD-L1/PD-1-mediated tumor immune escape. Mol Cancer. 2019;18:1–17. doi: 10.1186/s12943-018-0930-x. PubMed DOI PMC

Martinez-Bosch N, Vinaixa J, Navarro P. Immune evasion in pancreatic cancer: from mechanisms to therapy. Cancers (Basel) 2018;10(1):6. doi: 10.3390/cancers10010006. PubMed DOI PMC

Barsoum IB, Koti M, Siemens DR, Graham CH. Mechanisms of hypoxia-mediated immune escape in cancer. Cancer Res. 2014;74(24):7185–7190. doi: 10.1158/0008-5472.CAN-14-2598. PubMed DOI

Semenza GL. Intratumoral hypoxia and mechanisms of immune evasion mediated by hypoxia-inducible factors. Physiology (Bethesda) 2021;36(2):73–83. PubMed

Zheng H, Ning Y, Zhan Y, Liu S, Yang Y, Wen Q, et al. Co-expression of PD-L1 and HIF-1α predicts poor prognosis in patients with non-small cell lung cancer after surgery. J Cancer. 2021;12(7):2065–2072. doi: 10.7150/jca.53119. PubMed DOI PMC

Jahanban-Esfahlan R, de la Guardia M, Ahmadi D, Yousefi B. Modulating tumor hypoxia by nanomedicine for effective cancer therapy. J Cell Physiol. 2018;233(3):2019–2031. doi: 10.1002/jcp.25859. PubMed DOI

Bosco MC, D'Orazi G, Del Bufalo D. Targeting hypoxia in tumor: a new promising therapeutic strategy. J Exp Clin Cancer Res. 2020;39(1):1–3. doi: 10.1186/s13046-019-1487-2. PubMed DOI PMC

Zhang Q, Han Z, Zhu Y, Chen J, Li W. Role of hypoxia inducible factor-1 in cancer stem cells (Review) Mol Med Rep. 2021;23(1):17. PubMed PMC

Petrova V, Annicchiarico-Petruzzelli M, Melino G, Amelio I. The hypoxic tumour microenvironment. Oncogenesis. 2018;7:13. doi: 10.1038/s41389-017-0011-9. PubMed DOI PMC

Vito A, El-Sayes N, Mossman K. Hypoxia-driven immune escape in the tumor microenvironment. Cells. 2020;9(4):992. doi: 10.3390/cells9040992. PubMed DOI PMC

Liikanen I, Lauhan C, Quon S, Omilusik K, Phan AT, Bartrolí LB, et al. Hypoxia-inducible factor activity promotes antitumor effector function and tissue residency by CD8+ T cells. J Clin Invest. 2021;131(7):e143729. doi: 10.1172/JCI143729. PubMed DOI PMC

Dhalla NS, Mathur P, Mehta JL. Biochemical basis and therapeutic implications of angiogenesis. 2. New York: Springer; 2017.

Najafi M, Farhood B, Mortezaee K, Kharazinejad E, Majidpoor J, Ahadi R. Hypoxia in solid tumors: a key promoter of cancer stem cell (CSC) resistance. J Cancer Res Clin Oncol. 2020;146(1):19–31. doi: 10.1007/s00432-019-03080-1. PubMed DOI PMC

Balamurugan K. HIF-1 at the crossroads of hypoxia, inflammation, and cancer. Int J Cancer. 2016;138(5):1058–1066. doi: 10.1002/ijc.29519. PubMed DOI PMC

Wang J, Zeng H, Zhang HW, Han YW. The role of exosomal PD-L1 in tumor immunotherapy. Transl Oncol. 2021;14(5):1–7. PubMed PMC

Sun Y, Li L, Wu Y, Yang K. PD-1/PD-L1 in cardiovascular disease. Clin Chim Acta. 2020;505:26–30. doi: 10.1016/j.cca.2020.02.019. PubMed DOI

Chang YL, Yang CY, Lin MW, Wu CT, Yang PC. High co-expression of PD-L1 and HIF-1alpha correlates with tumour necrosis in pulmonary pleomorphic carcinoma. Eur J Cancer. 2016;60:125–135. doi: 10.1016/j.ejca.2016.03.012. PubMed DOI

Noman MZ, Desantis G, Janji B, Hasmim M, Karray S, Dessen P, et al. PD-L1 is a novel direct target of HIF-1alpha, and its blockade under hypoxia enhanced MDSC-mediated T cell activation. J Exp Med. 2014;211(5):781–790. doi: 10.1084/jem.20131916. PubMed DOI PMC

Zhao YT, Wang XX, Wu W, Long HX, Huang JN, Wang ZY, et al. EZH2 regulates PD-L1 expression via HIF-1 alpha in non-small cell lung cancer cells. Biochem Biophys Res Commun. 2019;517(2):201–209. doi: 10.1016/j.bbrc.2019.07.039. PubMed DOI

Deng J, Li JN, Sarde A, Lines JL, Lee YC, Qian DC, et al. Hypoxia-induced VISTA promotes the suppressive function of myeloid-derived suppressor cells in the tumor microenvironment. Cancer Immunol Res. 2019;7(7):1079–1090. doi: 10.1158/2326-6066.CIR-18-0507. PubMed DOI PMC

Fu Q, Xu L, Wang Y, Jiang Q, Liu Z, Zhang J, et al. Tumor-associated macrophage-derived interleukin-23 interlinks kidney cancer glutamine addiction with immune evasion. Eur Urol. 2019;75(5):752–763. doi: 10.1016/j.eururo.2018.09.030. PubMed DOI

Xiong Y, Liu L, Xia Y, Qi Y, Chen Y, Chen L, et al. Tumor infiltrating mast cells determine oncogenic HIF-2α-conferred immune evasion in clear cell renal cell carcinoma. Cancer Immunol Immunother. 2019;68(5):731–741. doi: 10.1007/s00262-019-02314-y. PubMed DOI PMC

Ren Z, Hu Y, Li G, Kang Y, Liu Y, Zhao H. HIF-1α induced long noncoding RNA FOXD2-AS1 promotes the osteosarcoma through repressing p21. Biomed Pharmacother. 2019;117:109104. doi: 10.1016/j.biopha.2019.109104. PubMed DOI

Xue M, Li X, Li Z, Chen W. Urothelial carcinoma associated 1 is a hypoxia-inducible factor-1α-targeted long noncoding RNA that enhances hypoxic bladder cancer cell proliferation, migration, and invasion. Tumour Biol. 2014;35(7):6901–6912. doi: 10.1007/s13277-014-1925-x. PubMed DOI

Jiang R, Tang J, Chen Y, Deng L, Ji J, Xie Y, et al. The long noncoding RNA lnc-EGFR stimulates T-regulatory cells differentiation thus promoting hepatocellular carcinoma immune evasion. Nat Commun. 2017;8:15129. doi: 10.1038/ncomms15129. PubMed DOI PMC

Evans JR, Feng FY, Chinnaiyan AM. The bright side of dark matter: lncRNAs in cancer. J Clin Invest. 2016;126(8):2775–2782. doi: 10.1172/JCI84421. PubMed DOI PMC

Joseph JP, Harishankar MK, Pillai AA, Devi A. Hypoxia induced EMT: A review on the mechanism of tumor progression and metastasis in OSCC. Oral Oncol. 2018;80:23–32. doi: 10.1016/j.oraloncology.2018.03.004. PubMed DOI

Rankin EB, Giaccia AJ. Hypoxic control of metastasis. Science. 2016;352(6282):175–180. doi: 10.1126/science.aaf4405. PubMed DOI PMC

Wang W, Chen H, Gao W, Wang S, Wu K, Lu C, et al. Girdin interaction with vimentin induces EMT and promotes the growth and metastasis of pancreatic ductal adenocarcinoma. Oncol Rep. 2020;44(2):637–649. doi: 10.3892/or.2020.7615. PubMed DOI PMC

Hu T, He N, Yang Y, Yin C, Sang N, Yang Q. DEC2 expression is positively correlated with HIF-1 activation and the invasiveness of human osteosarcomas. J Exp Clin Cancer Res. 2015;34(1):22. doi: 10.1186/s13046-015-0135-8. PubMed DOI PMC

Chen S, Zhang M, Xing L, Wang Y, Xiao Y, Wu Y. HIF-1α contributes to proliferation and invasiveness of neuroblastoma cells via SHH signaling. PLoS ONE. 2015;10(3):e0121115. doi: 10.1371/journal.pone.0121115. PubMed DOI PMC

Wang X, Dong J, Jia L, Zhao T, Lang M, Li Z, et al. HIF-2-dependent expression of stem cell factor promotes metastasis in hepatocellular carcinoma. Cancer Lett. 2017;393:113–124. doi: 10.1016/j.canlet.2017.01.032. PubMed DOI

Mabjeesh NJ, Post DE, Willard MT, Kaur B, Van Meir EG, Simons JW, et al. Geldanamycin induces degradation of hypoxia-inducible factor 1alpha protein via the proteosome pathway in prostate cancer cells. Cancer Res. 2002;62(9):2478–2482. PubMed

Jordan BF, Runquist M, Raghunand N, Gillies RJ, Tate WR, Powis G, et al. The thioredoxin-1 inhibitor 1-methylpropyl 2-imidazolyl disulfide (PX-12) decreases vascular permeability in tumor xenografts monitored by dynamic contrast enhanced magnetic resonance imaging. Clin Cancer Res. 2005;11(2):529–536. PubMed

Samanta D, Park Y, Ni X, Li H, Zahnow CA, Gabrielson E, et al. Chemotherapy induces enrichment of CD47(+)/CD73(+)/PDL1(+) immune evasive triple-negative breast cancer cells. Proc Natl Acad Sci U S A. 2018;115(6):E1239–E1248. doi: 10.1073/pnas.1718197115. PubMed DOI PMC

Luo W, Wang Y. Hypoxia mediates tumor malignancy and therapy resistance. Adv Exp Med Biol. 2019;1136:1–18. doi: 10.1007/978-3-030-12734-3_1. PubMed DOI

Seliger B. Molecular mechanisms of HLA class I-mediated immune evasion of human tumors and their role in resistance to immunotherapies. Hla. 2016;88(5):213–220. doi: 10.1111/tan.12898. PubMed DOI

Wu QH, Wang X, Nepovimova E, Miron A, Liu QY, Wang Y, et al. Trichothecenes: immunomodulatory effects, mechanisms, and anti-cancer potential. Arch Toxicol. 2017;91(12):3737–3785. doi: 10.1007/s00204-017-2118-3. PubMed DOI

Angeli JPF, Krysko DV, Conrad M. Ferroptosis at the crossroads of cancer-acquired drug resistance and immune evasion. Nat Rev Cancer. 2019;19(7):405–414. doi: 10.1038/s41568-019-0149-1. PubMed DOI

Barsoum IB, Smallwood CA, Siemens DR, Graham CH. A mechanism of hypoxia-mediated escape from adaptive immunity in cancer cells. Cancer Res. 2013;74(3):665–674. doi: 10.1158/0008-5472.CAN-13-0992. PubMed DOI

Rosenthal R, Cadieux EL, Salgado R, Al Bakir M, Moore DA, Hiley CT, et al. Neoantigen-directed immune escape in lung cancer evolution. Nature. 2019;567(7749):479–485. doi: 10.1038/s41586-019-1032-7. PubMed DOI PMC

Chabanon RM, Muirhead G, Krastev DB, Adam J, Morel D, Garrido M, et al. PARP inhibition enhances tumor cell-intrinsic immunity in ERCC1-deficient non-small cell lung cancer. J Clin Invest. 2019;129(3):1211–1228. doi: 10.1172/JCI123319. PubMed DOI PMC

Menter T, Tzankov A. Mechanisms of immune evasion and immune modulation by lymphoma cells. Front Oncol. 2018;8:54. doi: 10.3389/fonc.2018.00054. PubMed DOI PMC

Walsh SR, Simovic B, Chen L, Bastin D, Nguyen A, Stephenson K, et al. Endogenous T cells prevent tumor immune escape following adoptive T cell therapy. J Clin Invest. 2019;129(12):5400–5410. doi: 10.1172/JCI126199. PubMed DOI PMC

Ge Z, Wu S, Zhang Z, Ding SZ. Mechanism of tumor cells escaping from immune surveillance of NK cells. Immunopharmacol Immunotoxicol. 2020;42(3):187–198. doi: 10.1080/08923973.2020.1742733. PubMed DOI

Tran E, Ahmadzadeh M, Lu YC, Gros A, Turcotte S, Robbins PF, et al. Immunogenicity of somatic mutations in human gastrointestinal cancers. Science. 2015;350(6266):1387–1390. doi: 10.1126/science.aad1253. PubMed DOI PMC

Chaoul N, Tang A, Desrues B, Oberkampf M, Fayolle C, Ladant D, et al. Lack of MHC class II molecules favors CD8(+) T-cell infiltration into tumors associated with an increased control of tumor growth. OncoImmunology. 2018;7(3):1–15. doi: 10.1080/2162402X.2017.1404213. PubMed DOI PMC

Jhunjhunwala S, Hammer C, Delamarre L. Antigen presentation in cancer: insights into tumour immunogenicity and immune evasion. Nat Rev Cancer. 2021;21(5):298–312. doi: 10.1038/s41568-021-00339-z. PubMed DOI

Wei TF, Zhang J, Qin YH, Wu Y, Zhu L, Lu LK, et al. Increased expression of immunosuppressive molecules on intratumoral and circulating regulatory T cells in non-small-cell lung cancer patients. Am J Cancer Res. 2015;5(7):2190–2201. PubMed PMC

Li Z, Wang J, Zhang X, Liu P, Zhang X, Wang J, et al. Proinflammatory S100A8 induces PD-L1 expression in macrophages, mediating tumor immune escape. J Immunol (Baltimore Md: 1950) 2020;204(9):2589–2599. doi: 10.4049/jimmunol.1900753. PubMed DOI

Qiu S, Deng LH, Liao XY, Nie L, Qi F, Jin K, et al. Tumor-associated macrophages promote bladder tumor growth through PI3K/AKT signal induced by collagen. Cancer Sci. 2019;110(7):2110–2118. doi: 10.1111/cas.14078. PubMed DOI PMC

Eggermont LJ, Paulis LE, Tel J, Figdor CG. Towards efficient cancer immunotherapy: advances in developing artificial antigen-presenting cells. Trends Biotechnol. 2014;32(9):456–465. doi: 10.1016/j.tibtech.2014.06.007. PubMed DOI PMC

Altorki NK, Markowitz GJ, Gao DC, Port JL, Saxena A, Stiles B, et al. The lung microenvironment: an important regulator of tumour growth and metastasis. Nat Rev Cancer. 2019;19(1):9–31. doi: 10.1038/s41568-018-0081-9. PubMed DOI PMC

Chanmee T, Ontong P, Konno K, Itano N. Tumor-associated macrophages as major players in the tumor microenvironment. Cancers (Basel) 2014;6(3):1670–1690. doi: 10.3390/cancers6031670. PubMed DOI PMC

Xia X, Li R, Zhou P, Xing Z, Lu C, Long Z, et al. Decreased NSG3 enhances PD-L1 expression by Erk1/2 pathway to promote pancreatic cancer progress. Am J Cancer Res. 2021;11(3):916–929. PubMed PMC

Wen QX, Han T, Wang ZJ, Jiang SL. Role and mechanism of programmed death-ligand 1 in hypoxia-induced liver cancer immune escape. Oncol Lett. 2020;19(4):2595–2601. PubMed PMC

Qin JJ, Yan L, Zhang J, Zhang WD. STAT3 as a potential therapeutic target in triple negative breast cancer: a systematic review. J Exp Clin Cancer Res. 2019;38:1–16. doi: 10.1186/s13046-018-1018-6. PubMed DOI PMC

Bose D, Banerjee S, Chatterjee N, Das S, Saha M, Das SK. Inhibition of TGF-beta induced lipid droplets switches M2 macrophages to M1 phenotype. Toxicol Vitro. 2019;58:207–214. doi: 10.1016/j.tiv.2019.03.037. PubMed DOI

Tucci M, Passarelli A, Mannavola F, Felici C, Stucci LS, Cives M, et al. Immune system evasion as hallmark of melanoma progression: the role of dendritic cells. Front Oncol. 2019;9:14. doi: 10.3389/fonc.2019.01148. PubMed DOI PMC

Teng R, Wang Y, Lv N, Zhang D, Williamson RA, Lei L, et al. Hypoxia impairs NK cell cytotoxicity through SHP-1-mediated attenuation of STAT3 and ERK signaling pathways. J Immunol Res. 2020;2020:4598476. PubMed PMC

Dai X, Pi G, Yang SL, Chen GG, Liu LP, Dong HH. Association of PD-L1 and HIF-1alpha coexpression with poor prognosis in hepatocellular carcinoma. Transl Oncol. 2018;11(2):559–566. doi: 10.1016/j.tranon.2018.02.014. PubMed DOI PMC

Saleh R, Toor SM, Khalaf S, Elkord E. Breast cancer cells and PD-1/PD-L1 blockade upregulate the expression of PD-1, CTLA-4, TIM-3 and LAG-3 immune checkpoints in CD4(+) T cells. Vaccines. 2019;7(4):13. doi: 10.3390/vaccines7040149. PubMed DOI PMC

Sun C, Mezzadra R, Schumacher TN. Regulation and function of the PD-L1 checkpoint. Immunity. 2018;48(3):434–452. doi: 10.1016/j.immuni.2018.03.014. PubMed DOI PMC

Kalantari Khandani N, Ghahremanloo A, Hashemy SI. Role of tumor microenvironment in the regulation of PD-L1: a novel role in resistance to cancer immunotherapy. J Cell Physiol. 2020;235(10):6496–6506. doi: 10.1002/jcp.29671. PubMed DOI

Alsaab HO, Sau S, Alzhrani R, Tatiparti K, Bhise K, Kashaw SK, et al. PD-1 and PD-L1 checkpoint signaling inhibition for cancer immunotherapy: mechanism, combinations, and cinical outcome. Front Pharmacol. 2017;8:1–15. doi: 10.3389/fphar.2017.00561. PubMed DOI PMC

Ghanim B, Rosenmayr A, Stockhammer P, Vogl M, Celik A, Bas A, et al. Tumour cell PD-L1 expression is prognostic in patients with malignant pleural effusion: the impact of C-reactive protein and immune-checkpoint inhibition. Sci Rep. 2020;10(1):1–10. doi: 10.1038/s41598-020-62813-2. PubMed DOI PMC

Wen WX, Leong CO. Association of BRCA1-and BRCA2-deficiency with mutation burden, expression of PD-L1/ PD-1, immune infiltrates, and T cell-inflamed signature in breast cancer. PLoS ONE. 2019;14(4):1–16. PubMed PMC

Poggio M, Hu T, Pai C-C, Chu B, Belair CD, Chang A, et al. Suppression of exosomal PD-L1 induces systemic anti-tumor immunity and memory. Cell. 2019;177(2):414–427. doi: 10.1016/j.cell.2019.02.016. PubMed DOI PMC

Ma P, Xing MT, Han LM, Gan SL, Ma J, Wu FF, et al. High PD-L1 expression drives glycolysis via an Akt/mTOR/HIF-1 alpha axis in acute myeloid leukemia. Oncol Rep. 2020;43(3):999–1009. PubMed

Liang G, Li S, Du W, Ke Q, Cai J, Yang J. Hypoxia regulates CD44 expression via hypoxia-inducible factor-1α in human gastric cancer cells. Oncol Lett. 2017;13(2):967–972. doi: 10.3892/ol.2016.5473. PubMed DOI PMC

Chang WH, Lai AG. The hypoxic tumour microenvironment: a safe haven for immunosuppressive cells and a therapeutic barrier to overcome. Cancer Lett. 2020;487:34–44. doi: 10.1016/j.canlet.2020.05.011. PubMed DOI

Bhandari V, Hoey C, Liu LY, Lalonde E, Ray J, Livingstone J, et al. Molecular landmarks of tumor hypoxia across cancer types. Nature Genet. 2019;51(2):308–318. doi: 10.1038/s41588-018-0318-2. PubMed DOI

Al Tameemi W, Dale TP, Al-Jumaily RMK, Forsyth NR. Hypoxia-modified cancer cell metabolism. Front Cell Dev Biol. 2019;7:4. doi: 10.3389/fcell.2019.00004. PubMed DOI PMC

Schito L, Semenza GL. Hypoxia-inducible factors: master regulators of cancer progression. Trends Cancer. 2016;2(12):758–770. doi: 10.1016/j.trecan.2016.10.016. PubMed DOI

You L, Wu WD, Wang X, Fang LR, Adam V, Nepovimova E, et al. The role of hypoxia-inducible factor 1 in tumor immune evasion. Med Res Rev. 2021;41(3):1622–1643. doi: 10.1002/med.21771. PubMed DOI

Zheng YF, Chen HR, Zhao Y, Zhang XP, Liu JJ, Pan Y, et al. Knockdown of FBXO22 inhibits melanoma cell migration, invasion and angiogenesis via the HIF-1 alpha/VEGF pathway. Invest New Drugs. 2020;38(1):20–28. doi: 10.1007/s10637-019-00761-z. PubMed DOI

Surov A, Meyer HJ, Hoehn A-K, Winter K, Sabri O, Purz S. Associations between F-18 FDG-PET and complex histopathological parameters including tumor cell count and expression of KI 67, EGFR, VEGF, HIF-1, and p53 in head and neck squamous cell carcinoma. Mol Imag Biol. 2019;21(2):368–374. doi: 10.1007/s11307-018-1223-x. PubMed DOI

Noman MZ, Hasmim M, Messai Y, Terry S, Kieda C, Janji B, et al. Hypoxia: a key player in antitumor immune response. A review in the theme: cellular responses to hypoxia. Am J Physiol Cell Physiol. 2015;309(9):C569–579. doi: 10.1152/ajpcell.00207.2015. PubMed DOI PMC

Thews O, Riemann A. Tumor pH and metastasis: a malignant process beyond hypoxia. Cancer Metastasis Rev. 2019;38(1–2):113–129. doi: 10.1007/s10555-018-09777-y. PubMed DOI

Vaupel P, Multhoff G. Hypoxia-/HIF-1 alpha-driven factors of the tumor microenvironment impeding antitumor immune responses and promoting malignant progression. In: Thews O, LaManna JC, Harrison DK, editors. Advances in Experimental Medicine and Biology. Oxygen Transport to Tissue Xl. Cham: Springer; 2018. pp. 171–175. PubMed

Kouvaras E, Christoni Z, Siasios I, Malizos K, Koukoulis GK, Ioannou M. Hypoxia-inducible factor 1-alpha and vascular endothelial growth factor in cartilage tumors. Biotech Histochem. 2019;94(4):283–289. doi: 10.1080/10520295.2018.1556806. PubMed DOI

Zhou LY, Cha GF, Chen LY, Yang C, Xu D, Ge MH. HIF1 alpha/PD-L1 axis mediates hypoxia-induced cell apoptosis and tumor progression in follicular thyroid carcinoma. OncoTargets Ther. 2019;12:6461–6470. doi: 10.2147/OTT.S203724. PubMed DOI PMC

He J, Hu Y, Hu M, Li B. Development of PD-1/PD-L1 pathway in tumor immune microenvironment and treatment for non-small cell lung cancer. Sci Rep. 2015;5(1):13110. doi: 10.1038/srep13110. PubMed DOI PMC

Fujii T, Hirakata T, Kurozumi S, Tokuda S, Nakazawa Y, Obayashi S, et al. VEGF-A is associated with the degree of TILs and PD-L1 expression in primary breast cancer. In Vivo. 2020;34(5):2641–2646. doi: 10.21873/invivo.12082. PubMed DOI PMC

Kaur S, Chang T, Singh SP, Lim L, Mannan P, Garfield SH, et al. CD47 signaling regulates the immunosuppressive activity of VEGF in T cells. J Immunol. 2014;193(8):3914–3924. doi: 10.4049/jimmunol.1303116. PubMed DOI PMC

Zhang H, Lu H, Xiang L, Bullen JW, Zhang C, Samanta D, et al. HIF-1 regulates CD47 expression in breast cancer cells to promote evasion of phagocytosis and maintenance of cancer stem cells. Proc Natl Acad Sci USA. 2015;112(45):E6215–6223. PubMed PMC

Janker L, Mayer RL, Bileck A, Kreutz D, Mader JC, Utpatel K, et al. Metabolic, anti-apoptotic and immune evasion strategies of primary human myeloma cells indicate adaptations to hypoxia. Mol Cell Proteomics. 2019;18(5):936–953. doi: 10.1074/mcp.RA119.001390. PubMed DOI PMC

Semenza GL. Pharmacologic targeting of hypoxia-inducible factors. Annu Rev Pharmacol Toxicol. 2019;59:379–403. doi: 10.1146/annurev-pharmtox-010818-021637. PubMed DOI

Koyasu S, Kobayashi M, Goto Y, Hiraoka M, Harada H. Regulatory mechanisms of hypoxia-inducible factor 1 activity: two decades of knowledge. Cancer Sci. 2018;109(3):560–571. doi: 10.1111/cas.13483. PubMed DOI PMC

Giatromanolaki A, Koukourakis IM, Balaska K, Mitrakas AG, Harris AL, Koukourakis MI. Programmed death-1 receptor (PD-1) and PD-ligand-1 (PD-L1) expression in non-small cell lung cancer and the immune-suppressive effect of anaerobic glycolysis. Med Oncol. 2019;36(9):1–12. doi: 10.1007/s12032-019-1299-4. PubMed DOI

Noman MZ, Chouaib S. Targeting hypoxia at the forefront of anticancer immune responses. OncoImmunology. 2014;3(12):1–3. doi: 10.4161/21624011.2014.954463. PubMed DOI PMC

Bailly C. Regulation of PD-L1 expression on cancer cells with ROS-modulating drugs. Life Sci. 2020;246:1–8. doi: 10.1016/j.lfs.2020.117403. PubMed DOI

Le Mercier I, Chen W, Lines JL, Day M, Li J, Sergent P, et al. VISTA regulates the development of protective antitumor immunity. Cancer Res. 2014;74(7):1933–1944. doi: 10.1158/0008-5472.CAN-13-1506. PubMed DOI PMC

Lu Y, Hu J, Sun W, Duan X, Chen X. Hypoxia-mediated immune evasion of pancreatic carcinoma cells. Mol Med Rep. 2015;11(5):3666–3672. doi: 10.3892/mmr.2015.3144. PubMed DOI

Siemens DR, Hu NP, Sheikhi AK, Chung E, Frederiksen LJ, Pross H, et al. Hypoxia increases tumor cell shedding of MHC class I chain-related molecule: role of nitric oxide. Cancer Res. 2008;68(12):4746–4753. doi: 10.1158/0008-5472.CAN-08-0054. PubMed DOI

Ren L, Yu Y, Wang L, Zhu Z, Lu R, Yao Z. Hypoxia-induced CCL28 promotes recruitment of regulatory T cells and tumor growth in liver cancer. Oncotarget. 2016;7(46):75763–75773. doi: 10.18632/oncotarget.12409. PubMed DOI PMC

Takeuchi Y, Nishikawa H. Roles of regulatory T cells in cancer immunity. Int Immunol. 2016;28(8):401–409. doi: 10.1093/intimm/dxw025. PubMed DOI PMC

Chen CH, Li SX, Xiang LX, Mu HQ, Wang SB, Yu KY. HIF-1 alpha induces immune escape of prostate cancer by regulating NCR1/NKp46 signaling through miR-224. Biochem Biophys Res Commun. 2018;503(1):228–234. doi: 10.1016/j.bbrc.2018.06.007. PubMed DOI

Robinson CM, Poon BPK, Kano Y, Pluthero FG, Kahr WHA, Ohh M. A hypoxia-inducible HIF1-GAL3ST1-sulfatide axis enhances ccRCC immune evasion via increased tumor cell-platelet binding. Mol Cancer Res. 2019;17(11):2306–2317. doi: 10.1158/1541-7786.MCR-19-0461. PubMed DOI

Jin KT, Yao JY, Fang XL, Di H, Ma YY. Roles of lncRNAs in cancer: Focusing on angiogenesis. Life Sci. 2020;252:1–9. doi: 10.1016/j.lfs.2020.117647. PubMed DOI

Liu W, Li S. LncRNA ILF3-AS1 promotes the progression of colon adenocarcinoma cells through the miR-619-5p/CAMK1D axis. Onco Targets Ther. 2021;14:1861–1872. doi: 10.2147/OTT.S296441. PubMed DOI PMC

Shih JW, Kung HJ. Long non-coding RNA and tumor hypoxia: new players ushered toward an old arena. J Biomed Sci. 2017;24:1–19. doi: 10.1186/s12929-017-0358-4. PubMed DOI PMC

Shih JW, Chiang WF, Wu ATH, Wu MH, Wang LY, Yu YL, et al. Long noncoding RNA LncHIFCAR/MIR31HG is a HIF-1 alpha co-activator driving oral cancer progression. Nat Commun. 2017;8:1–16. doi: 10.1038/ncomms15874. PubMed DOI PMC

Ren ZP, Hu YC, Li GS, Kang YX, Liu YC, Zhao HJ. HIF-1 alpha induced long noncoding RNA FOXD2-AS1 promotes the osteosarcoma through repressing p21. Biomed Pharmacother. 2019;117:1–6. PubMed

Wang Y, Cao L, Wang Q, Huang J, Xu S. LncRNA FOXD2-AS1 induces chondrocyte proliferation through sponging miR-27a-3p in osteoarthritis. Artif Cells Nanomed Biotechnol. 2019;47(1):1241–1247. doi: 10.1080/21691401.2019.1596940. PubMed DOI

Ni W, Xia Y, Bi Y, Wen F, Hu D, Luo L. FoxD2-AS1 promotes glioma progression by regulating miR-185-5P/HMGA2 axis and PI3K/AKT signaling pathway. Aging (Albany NY) 2019;11(5):1427–1439. doi: 10.18632/aging.101843. PubMed DOI PMC

Ye JJ, Liu JD, Tang T, Xin L, Bao X, Yan YK. miR-4306 inhibits the malignant behaviors of colorectal cancer by regulating lncRNA FoxD2-AS1. Mol Med Rep. 2021;24(4):10. doi: 10.3892/mmr.2021.12362. PubMed DOI PMC

Rong L, Zhao R, Lu J. Highly expressed long non-coding RNA FOXD2-AS1 promotes non-small cell lung cancer progression via Wnt/β-catenin signaling. Biochem Biophys Res Commun. 2017;484(3):586–591. doi: 10.1016/j.bbrc.2017.01.141. PubMed DOI

Zhao QJ, Zhang J, Xu L, Liu FF. Identification of a five-long non-coding RNA signature to improve the prognosis prediction for patients with hepatocellular carcinoma. World J Gastroenterol. 2018;24(30):3426–3439. doi: 10.3748/wjg.v24.i30.3426. PubMed DOI PMC

Chang Y, Zhang J, Zhou C, Qiu G, Wang G, Wang S, et al. Long non-coding RNA FOXD2-AS1 plays an oncogenic role in hepatocellular carcinoma by targeting miR-206. Oncol Rep. 2018;40(6):3625–3634. PubMed

Xue M, Chen W, Xiang A, Wang R, Chen H, Pan J, et al. Hypoxic exosomes facilitate bladder tumor growth and development through transferring long non-coding RNA-UCA1. Mol Cancer. 2017;16(1):143. doi: 10.1186/s12943-017-0714-8. PubMed DOI PMC

Jiang RQ, Tang JW, Chen Y, Deng L, Ji J, Xie Y, et al. The long noncoding RNA lnc-EGFR stimulates T-regulatory cells differentiation thus promoting hepatocellular carcinoma immune evasion. Nat Commun. 2017;8:1–15. doi: 10.1038/s41467-016-0009-6. PubMed DOI PMC

Huang D, Chen JN, Yang LB, Ouyang Q, Li JQ, Lao LY, et al. NKILA lncRNA promotes tumor immune evasion by sensitizing T cells to activation-induced cell death. Nat Immunol. 2018;19(10):1112–1125. doi: 10.1038/s41590-018-0207-y. PubMed DOI

Zhao LN, Liu Y, Zhang JB, Liu Y, Qi Q. LncRNA SNHG14/miR-5590-3p/ZEB1 positive feedback loop promoted diffuse large B cell lymphoma progression and immune evasion through regulating PD-1/PD-L1 checkpoint. Cell Death Dis. 2019;10:1–15. doi: 10.1038/s41419-018-1236-z. PubMed DOI PMC

Palazon A, Goldrath AW, Nizet V, Johnson RS. HIF transcription factors, inflammation, and immunity. Immunity. 2014;41(4):518–528. doi: 10.1016/j.immuni.2014.09.008. PubMed DOI PMC

Yuen VW, Wong CC. Hypoxia-inducible factors and innate immunity in liver cancer. J Clin Invest. 2020;130(10):5052–5062. doi: 10.1172/JCI137553. PubMed DOI PMC

Colgan SP, Furuta GT, Taylor CT. Hypoxia and innate immunity: keeping up with the HIFsters. Annu Rev Immunol. 2020;38:341–363. doi: 10.1146/annurev-immunol-100819-121537. PubMed DOI PMC

Rius J, Guma M, Schachtrup C, Akassoglou K, Zinkernagel AS, Nizet V, et al. NF-kappaB links innate immunity to the hypoxic response through transcriptional regulation of HIF-1alpha. Nature. 2008;453(7196):807–811. doi: 10.1038/nature06905. PubMed DOI PMC

McGettrick AF, O'Neill LAJ. The role of HIF in immunity and inflammation. Cell Metab. 2020;32(4):524–536. doi: 10.1016/j.cmet.2020.08.002. PubMed DOI

Imtiyaz HZ, Williams EP, Hickey MM, Patel SA, Durham AC, Yuan LJ, et al. Hypoxia-inducible factor 2alpha regulates macrophage function in mouse models of acute and tumor inflammation. J Clin Invest. 2010;120(8):2699–2714. doi: 10.1172/JCI39506. PubMed DOI PMC

Noman MZ, Janji B, Hu S, Wu JC, Martelli F, Bronte V, et al. Tumor-promoting effects of myeloid-derived suppressor cells are potentiated by hypoxia-induced expression of miR-210. Cancer Res. 2015;75(18):3771–3787. doi: 10.1158/0008-5472.CAN-15-0405. PubMed DOI

Zhou SL, Zhou ZJ, Hu ZQ, Huang XW, Wang Z, Chen EB, et al. Tumor-associated neutrophils recruit macrophages and T-regulatory cells to promote progression of hepatocellular carcinoma and resistance to sorafenib. Gastroenterology. 2016;150(7):1646–1658.e1617. doi: 10.1053/j.gastro.2016.02.040. PubMed DOI

Liang W, Ferrara N. The complex role of neutrophils in tumor angiogenesis and metastasis. Cancer Immunol Res. 2016;4(2):83–91. doi: 10.1158/2326-6066.CIR-15-0313. PubMed DOI

Kuschel A, Simon P, Tug S. Functional regulation of HIF-1α under normoxia–is there more than post-translational regulation? J Cell Physiol. 2012;227(2):514–524. doi: 10.1002/jcp.22798. PubMed DOI

Kachamakova-Trojanowska N, Podkalicka P, Bogacz T, Barwacz S, Józkowicz A, Dulak J, et al. HIF-1 stabilization exerts anticancer effects in breast cancer cells in vitro and in vivo. Biochem Pharmacol. 2020;175:113922. doi: 10.1016/j.bcp.2020.113922. PubMed DOI

Bilton RL, Booker GW. The subtle side to hypoxia inducible factor (HIFalpha) regulation. Eur J Biochem. 2003;270(5):791–798. doi: 10.1046/j.1432-1033.2003.03446.x. PubMed DOI

Meng X, Grötsch B, Luo Y, Knaup KX, Wiesener MS, Chen XX, et al. Hypoxia-inducible factor-1α is a critical transcription factor for IL-10-producing B cells in autoimmune disease. Nat Commun. 2018;9(1):251. doi: 10.1038/s41467-017-02683-x. PubMed DOI PMC

Pezzuto A, Carico E. Role of HIF-1 in cancer progression: novel insights. A review. Curr Mol Med. 2018;18(6):343–351. doi: 10.2174/1566524018666181109121849. PubMed DOI

Krieg M, Haas R, Brauch H, Acker T, Flamme I, Plate KH. Up-regulation of hypoxia-inducible factors HIF-1alpha and HIF-2alpha under normoxic conditions in renal carcinoma cells by von Hippel-Lindau tumor suppressor gene loss of function. Oncogene. 2000;19(48):5435–5443. doi: 10.1038/sj.onc.1203938. PubMed DOI

Shah T, Krishnamachary B, Wildes F, Mironchik Y, Kakkad SM, Jacob D, et al. HIF isoforms have divergent effects on invasion, metastasis, metabolism and formation of lipid droplets. Oncotarget. 2015;6(29):28104–28119. doi: 10.18632/oncotarget.4612. PubMed DOI PMC

Lin MC, Lin JJ, Hsu CL, Juan HF, Lou PJ, Huang MC. GATA3 interacts with and stabilizes HIF-1α to enhance cancer cell invasiveness. Oncogene. 2017;36(30):4243–4252. doi: 10.1038/onc.2017.8. PubMed DOI PMC

Hayakawa H, Shibasaki F. Biochemical basis and therapeutic implications of angiogenesis (2017).

Liu ZJ, Semenza GL, Zhang HF. Hypoxia-inducible factor 1 and breast cancer metastasis. J Zhejiang Univ Sci B. 2015;16(1):32–43. doi: 10.1631/jzus.B1400221. PubMed DOI PMC

Chen Y, Zhang B, Bao L, Jin L, Yang M, Peng Y, et al. ZMYND8 acetylation mediates HIF-dependent breast cancer progression and metastasis. J Clin Invest. 2018;128(5):1937–1955. doi: 10.1172/JCI95089. PubMed DOI PMC

Rankin EB, Fuh KC, Castellini L, Viswanathan K, Finger EC, Diep AN, et al. Direct regulation of GAS6/AXL signaling by HIF promotes renal metastasis through SRC and MET. Proc Natl Acad Sci USA. 2014;111(37):13373–13378. doi: 10.1073/pnas.1404848111. PubMed DOI PMC

Thomas S, Harding MA, Smith SC, Overdevest JB, Nitz MD, Frierson HF, et al. CD24 is an effector of HIF-1-driven primary tumor growth and metastasis. Cancer Res. 2012;72(21):5600–5612. doi: 10.1158/0008-5472.CAN-11-3666. PubMed DOI PMC

Zhu Y, Tan J, Xie H, Wang J, Meng X, Wang R. HIF-1α regulates EMT via the Snail and β-catenin pathways in paraquat poisoning-induced early pulmonary fibrosis. J Cell Mol Med. 2016;20(4):688–697. doi: 10.1111/jcmm.12769. PubMed DOI PMC

Chen T, You Y, Jiang H, Wang ZZ. Epithelial-mesenchymal transition (EMT): a biological process in the development, stem cell differentiation, and tumorigenesis. J Cell Physiol. 2017;232(12):3261–3272. doi: 10.1002/jcp.25797. PubMed DOI PMC

De Francesco EM, Maggiolini M, Musti AM. Crosstalk between Notch, HIF-1α and GPER in breast cancer EMT. Int J Mol Sci. 2018;19(7):2011. doi: 10.3390/ijms19072011. PubMed DOI PMC

Yan Y, Liu F, Han L, Zhao L, Chen J, Olopade OI, et al. HIF-2α promotes conversion to a stem cell phenotype and induces chemoresistance in breast cancer cells by activating Wnt and Notch pathways. J Exp Clin Cancer Res. 2018;37(1):256. doi: 10.1186/s13046-018-0925-x. PubMed DOI PMC

Asgarova A, Asgarov K, Godet Y, Peixoto P, Nadaradjane A, Boyer-Guittaut M, et al. PD-L1 expression is regulated by both DNA methylation and NF-kB during EMT signaling in non-small cell lung carcinoma. OncoImmunology. 2018;7(5):e1423170. doi: 10.1080/2162402X.2017.1423170. PubMed DOI PMC

Triaca V, Carito V, Fico E, Rosso P, Fiore M, Ralli M, et al. Cancer stem cells-driven tumor growth and immune escape: the Janus face of neurotrophins. Aging-Us. 2019;11(23):11770–11792. doi: 10.18632/aging.102499. PubMed DOI PMC

Oliveira-Costa JP, Zanetti JS, Silveira GG, Soave DF, Oliveira LR, Zorgetto VA, et al. Differential expression of HIF-1α in CD44+CD24-/low breast ductal carcinomas. Diagn Pathol. 2011;6:73. doi: 10.1186/1746-1596-6-73. PubMed DOI PMC

Zhang C, Samanta D, Lu H, Bullen JW, Zhang H, Chen I, et al. Hypoxia induces the breast cancer stem cell phenotype by HIF-dependent and ALKBH5-mediated m6A-demethylation of NANOG mRNA. Proc Natl Acad Sci USA. 2016;113(14):E2047–2056. doi: 10.1073/pnas.1602883113. PubMed DOI PMC

Liedtke S, Stephan M, Kögler G. Oct4 expression revisited: potential pitfalls for data misinterpretation in stem cell research. Biol Chem. 2008;389(7):845–850. doi: 10.1515/BC.2008.098. PubMed DOI

Seidel S, Garvalov BK, Wirta V, von Stechow L, Schänzer A, Meletis K, et al. A hypoxic niche regulates glioblastoma stem cells through hypoxia inducible factor 2 alpha. Brain. 2010;133(Pt 4):983–995. doi: 10.1093/brain/awq042. PubMed DOI

Nusblat LM, Tanna S, Roth CM. Gene silencing of HIF-2α disrupts glioblastoma stem cell phenotype. Cancer Drug Resist. 2020;3(2):199–208. PubMed PMC

Pinzón-Daza ML, Cuellar-Saenz Y, Nualart F, Ondo-Mendez A, Del Riesgo L, Castillo-Rivera F, et al. Oxidative stress promotes doxorubicin-induced Pgp and BCRP expression in colon cancer cells under hypoxic conditions. J Cell Biochem. 2017;118(7):1868–1878. doi: 10.1002/jcb.25890. PubMed DOI

Wang K, Zhu X, Zhang K, Yin YX, Chen Y, Zhang T. Interleukin-6 contributes to chemoresistance in MDA-MB-231 cells via targeting HIF-1 alpha. J Biochem Mol Toxicol. 2018;32(3):1–7. doi: 10.1002/jbt.22039. PubMed DOI

Tang YA, Chen YF, Bao Y, Mahara S, Yatim S, Oguz G, et al. Hypoxic tumor microenvironment activates GLI2 via HIF-1 alpha and TGF-beta 2 to promote chemoresistance in colorectal cancer. Proc Natl Acad Sci USA. 2018;115(26):E5990–E5999. doi: 10.1073/pnas.1801348115. PubMed DOI PMC

Okazaki M, Fushida S, Tsukada T, Kinoshita J, Oyama K, Miyashita T, et al. The effect of HIF-1α and PKM1 expression on acquisition of chemoresistance. Cancer Manag Res. 2018;10:1865–1874. doi: 10.2147/CMAR.S166136. PubMed DOI PMC

Zhao Q, Li Y, Tan BB, Fan LQ, Yang PG, Tian Y. HIF-1α induces multidrug resistance in gastric cancer cells by inducing miR-27a. PLoS ONE. 2015;10(8):e0132746. doi: 10.1371/journal.pone.0132746. PubMed DOI PMC

Gao XZ, Wang GN, Zhao WG, Han J, Diao CY, Wang XH, et al. Blocking OLFM4/HIF-1α axis alleviates hypoxia-induced invasion, epithelial-mesenchymal transition, and chemotherapy resistance in non-small-cell lung cancer. J Cell Physiol. 2019;234(9):15035–15043. doi: 10.1002/jcp.28144. PubMed DOI

Wu HM, Jiang ZF, Ding PS, Shao LJ, Liu RY. Hypoxia-induced autophagy mediates cisplatin resistance in lung cancer cells. Sci Rep. 2015;5:12291. doi: 10.1038/srep12291. PubMed DOI PMC

Wen YA, Stevens PD, Gasser ML, Andrei R, Gao T. Downregulation of PHLPP expression contributes to hypoxia-induced resistance to chemotherapy in colon cancer cells. Mol Cell Biol. 2013;33(22):4594–4605. doi: 10.1128/MCB.00695-13. PubMed DOI PMC

Rankin EB, Biju MP, Liu Q, Unger TL, Rha J, Johnson RS, et al. Hypoxia-inducible factor-2 (HIF-2) regulates hepatic erythropoietin in vivo. J Clin Invest. 2007;117(4):1068–1077. doi: 10.1172/JCI30117. PubMed DOI PMC

Wigerup C, Påhlman S, Bexell D. Therapeutic targeting of hypoxia and hypoxia-inducible factors in cancer. Pharmacol Ther. 2016;164:152–169. doi: 10.1016/j.pharmthera.2016.04.009. PubMed DOI

Thompson JM, Landman J, Razorenova OV. Targeting the RhoGTPase/ROCK pathway for the treatment of VHL/HIF pathway-driven cancers. Small GTPases. 2020;11(1):32–38. doi: 10.1080/21541248.2017.1336193. PubMed DOI PMC

Murugesan T, Rajajeyabalachandran G, Kumar S, Nagaraju S, Jegatheesan SK. Targeting HIF-2 as therapy for advanced cancers. Drug Discov Today. 2018;23(7):1444–1451. doi: 10.1016/j.drudis.2018.05.003. PubMed DOI

Semenza GL. Targeting HIF-1 for cancer therapy. Nat Rev Cancer. 2003;3(10):721–732. doi: 10.1038/nrc1187. PubMed DOI

Isaacs JS, Jung YJ, Mimnaugh EG, Martinez A, Cuttitta F, Neckers LM. Hsp90 regulates a von Hippel Lindau-independent hypoxia-inducible factor-1 alpha-degradative pathway. J Biol Chem. 2002;277(33):29936–29944. doi: 10.1074/jbc.M204733200. PubMed DOI

Zagzag D, Nomura M, Friedlander DR, Blanco CY, Gagner JP, Nomura N, et al. Geldanamycin inhibits migration of glioma cells in vitro: a potential role for hypoxia-inducible factor (HIF-1alpha) in glioma cell invasion. J Cell Physiol. 2003;196(2):394–402. doi: 10.1002/jcp.10306. PubMed DOI

Zhu Y, Zang Y, Zhao F, Li Z, Zhang J, Fang L, et al. Inhibition of HIF-1α by PX-478 suppresses tumor growth of esophageal squamous cell cancer in vitro and in vivo. Am J Cancer Res. 2017;7(5):1198–1212. PubMed PMC

Welsh SJ, Williams RR, Birmingham A, Newman DJ, Kirkpatrick DL, Powis G. The thioredoxin redox inhibitors 1-methylpropyl 2-imidazolyl disulfide and pleurotin inhibit hypoxia-induced factor 1alpha and vascular endothelial growth factor formation. Mol Cancer Ther. 2003;2(3):235–243. PubMed

Courtney KD, Ma Y, Diazde Leon A, Christie A, Xie Z, Woolford L, et al. HIF-2 complex dissociation, target inhibition, and acquired resistance with PT2385, a first-in-class HIF-2 inhibitor, in patients with clear cell renal cell carcinoma. Clin Cancer Res. 2020;26(4):793–803. doi: 10.1158/1078-0432.CCR-19-1459. PubMed DOI PMC

Cho H, Du X, Rizzi JP, Liberzon E, Chakraborty AA, Gao W, et al. On-target efficacy of a HIF-2α antagonist in preclinical kidney cancer models. Nature. 2016;539(7627):107–111. doi: 10.1038/nature19795. PubMed DOI PMC

Terzuoli E, Puppo M, Rapisarda A, Uranchimeg B, Cao L, Burger AM, et al. Aminoflavone, a ligand of the aryl hydrocarbon receptor, inhibits HIF-1alpha expression in an AhR-independent fashion. Cancer Res. 2010;70(17):6837–6848. doi: 10.1158/0008-5472.CAN-10-1075. PubMed DOI PMC

Lee K, Zhang H, Qian DZ, Rey S, Liu JO, Semenza GL. Acriflavine inhibits HIF-1 dimerization, tumor growth, and vascularization. Proc Natl Acad Sci USA. 2009;106(42):17910–17915. doi: 10.1073/pnas.0909353106. PubMed DOI PMC

Cook KM, Hilton ST, Mecinovic J, Motherwell WB, Figg WD, Schofield CJ. Epidithiodiketopiperazines block the interaction between hypoxia-inducible factor-1alpha (HIF-1alpha) and p300 by a zinc ejection mechanism. J Biol Chem. 2009;284(39):26831–26838. doi: 10.1074/jbc.M109.009498. PubMed DOI PMC

Carroll JL, Nielsen LL, Pruett SB, Mathis JM. The role of natural killer cells in adenovirus-mediated p53 gene therapy. Mol Cancer Ther. 2001;1(1):49–60. PubMed

Yamakuchi M, Lotterman CD, Bao C, Hruban RH, Karim B, Mendell JT, et al. P53-induced microRNA-107 inhibits HIF-1 and tumor angiogenesis. Proc Natl Acad Sci USA. 2010;107(14):6334–6339. doi: 10.1073/pnas.0911082107. PubMed DOI PMC

Choi SH, Kwon OJ, Park JY, Kim DY, Ahn SH, Kim SU, et al. Inhibition of tumour angiogenesis and growth by small hairpin HIF-1α and IL-8 in hepatocellular carcinoma. Liver Int. 2014;34(4):632–642. doi: 10.1111/liv.12375. PubMed DOI

Newest 20 citations...

See more in
Medvik | PubMed

The role of cellular senescence in neurodegenerative diseases

. 2024 Aug ; 98 (8) : 2393-2408. [epub] 20240515

Find record

Citation metrics

Loading data ...

Archiving options

Loading data ...