Role of hypoxia‑inducible factor‑2α in lung cancer (Review)
- Authors:
- Wen-Jun Wang
- Chao Ouyang
- Bin Yu
- Chong Chen
- Xiao-Feng Xu
- Xiao-Qun Ye
-
Affiliations: Department of Respiratory Diseases, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China - Published online on: March 9, 2021 https://doi.org/10.3892/or.2021.8008
- Article Number: 57
This article is mentioned in:
Abstract
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 | |
Ema M, Taya S, Yokotani N, Sogawa K, Matsuda Y and 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. 94:4273–4278. 1997. View Article : Google Scholar : PubMed/NCBI | |
Wiesener MS, Turley H, Allen WE, Willam C, Eckardt KU, Talks KL, Wood SM, Gatter KC, Harris AL, Pugh CW, et al: Induction of endothelial PAS domain protein-1 by hypoxia: Characterization and comparison with hypoxia-inducible factor-1alpha. Blood. 92:2260–2268. 1998. View Article : Google Scholar : PubMed/NCBI | |
Favier J, Kempf H, Corvol P and Gasc JM: Cloning and expression pattern of EPAS1 in the chicken embryo. Colocalization with tyrosine hydroxylase. FEBS Lett. 462:19–24. 1999. View Article : Google Scholar : PubMed/NCBI | |
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 | |
Blancher C, Moore JW, Talks KL, Houlbrook S and Harris AL: Relationship of hypoxia-inducible factor (HIF)-1alpha and HIF-2alpha expression to vascular endothelial growth factor induction and hypoxia survival in human breast cancer cell lines. Cancer Res. 60:7106–7113. 2000.PubMed/NCBI | |
Rajakumar A, Whitelock KA, Weissfeld LA, Daftary AR, Markovic N and Conrad KP: Selective overexpression of the hypoxia-inducible transcription factor, HIF-2alpha, in placentas from women with preeclampsia. Biol Reprod. 64:499–506. 2001. View Article : Google Scholar : PubMed/NCBI | |
Brusselmans K, Bono F, Maxwell P, Dor Y, Dewerchin M, Collen D, Herbert JM and Carmeliet P: Hypoxia-inducible factor-2alpha (HIF-2alpha) is involved in the apoptotic response to hypoglycemia but not to hypoxia. J Biol Chem. 276:39192–39196. 2001. View Article : Google Scholar : PubMed/NCBI | |
Chen J, Chen J, Huang J, Li Z, Gong Y, Zou B, Liu X, Ding L, Li P, Zhu Z, et al: HIF-2α upregulation mediated by hypoxia promotes NAFLD-HCC progression by activating lipid synthesis via the PI3K-AKT-mTOR pathway. Aging (Albany NY). 11:10839–10860. 2019. View Article : Google Scholar : PubMed/NCBI | |
Saito T, Fukai A, Mabuchi A, Ikeda T, Yano F, Ohba S, Nishida N, Akune T, Yoshimura N, Nakagawa T, et al: Transcriptional regulation of endochondral ossification by HIF-2alpha during skeletal growth and osteoarthritis development. Nat Med. 16:678–686. 2010. View Article : Google Scholar : PubMed/NCBI | |
Chen W, Hill H, Christie A, Kim MS, Holloman E, Pavia-Jimenez A, Homayoun F, Ma Y, Patel N, Yell P, et al: Targeting renal cell carcinoma with a HIF-2 antagonist. Nature. 539:112–117. 2016. View Article : Google Scholar : PubMed/NCBI | |
Choueiri TK and Kaelin WG Jr: Targeting the HIF2-VEGF axis in renal cell carcinoma. Nat Med. 26:1519–1530. 2020. View Article : Google Scholar : PubMed/NCBI | |
Sun DR, Wang ZJ, Zheng QC and Zhang HX: Exploring the inhibition mechanism on HIF-2 by inhibitor PT2399 and 0X3 using molecular dynamics simulations. J Mol Recognit. 31:e27302018. View Article : Google Scholar : PubMed/NCBI | |
Sasagawa T, Nagamatsu T, Morita K, Mimura N, Iriyama T, Fujii T and Shibuya M: HIF-2α, but not HIF-1α, mediates hypoxia-induced up-regulation of Flt-1 gene expression in placental trophoblasts. Sci Rep. 8:173752018. View Article : Google Scholar : PubMed/NCBI | |
Spirina LV, Yurmazov ZA, Gorbunov AK, Usynin EA, Lushnikova NA and Kovaleva IV: Molecular protein and expression profile in the primary tumors of clear cell renal carcinoma and metastases. Cells. 9:16802020. View Article : Google Scholar | |
Cui XG, Han ZT, He SH, Wu XD, Chen TR, Shao CH, Chen DL, Su N, Chen YM, Wang T, et al: HIF1/2α mediates hypoxia-induced LDHA expression in human pancreatic cancer cells. Oncotarget. 8:24840–24852. 2017. View Article : Google Scholar : PubMed/NCBI | |
He C, Sun XP, Qiao H, Jiang X, Wang D, Jin X, Dong X, Wang J, Jiang H and Sun X: Downregulating hypoxia-inducible factor-2α improves the efficacy of doxorubicin in the treatment of hepatocellular carcinoma. Cancer Sci. 103:528–534. 2012. View Article : Google Scholar : PubMed/NCBI | |
Cleven AH, Wouters BG, Schutte B, Spiertz AJ, van Engeland M and de Bruïne AP: 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. 99:727–733. 2008. View Article : Google Scholar : PubMed/NCBI | |
Kong X, Zhao Y, Li X, Tao Z, Hou M and Ma H: Overexpression of HIF-2α-dependent NEAT1 promotes the progression of non-small cell lung cancer through miR-101-3p/SOX9/Wnt/β-catenin signal pathway. Cell Physiol Biochem. 52:368–381. 2019. View Article : Google Scholar : PubMed/NCBI | |
Påhlman S and Mohlin S: Hypoxia and hypoxia-inducible factors in neuroblastoma. Cell Tissue Res. 372:269–275. 2018. View Article : Google Scholar : PubMed/NCBI | |
Zhao D, Wang S, Chu X and Han D: LncRNA HIF2PUT inhibited osteosarcoma stem cells proliferation, migration and invasion by regulating HIF2 expression. Artif Cells Nanomed Biotechnol. 47:1342–1348. 2019. View Article : Google Scholar : PubMed/NCBI | |
Wang Y, Chen Y, Bao L, Zhang B, Wang JE, Kumar A, Xing C, Wang Y and Luo W: CHD4 promotes breast cancer progression as a coactivator of hypoxia-inducible factors. Cancer Res. 80:3880–3891. 2020. View Article : Google Scholar : PubMed/NCBI | |
Onita T, Ji PG, Xuan JW, Sakai H, Kanetake H, Maxwell PH, Fong GH, Gabril MY, Moussa M and Chin JL: Hypoxia-induced, perinecrotic expression of endothelial Per-ARNT-Sim domain protein-1/hypoxia-inducible factor-2alpha correlates with tumor progression, vascularization, and focal macrophage infiltration in bladder cancer. Clin Cancer Res. 8:471–480. 2002.PubMed/NCBI | |
Lim E, Kuo CC, Tu HF and Yang CC: The prognosis outcome of oral squamous cell carcinoma using HIF-2alpha. J Chin Med Assoc. 80:651–656. 2017. View Article : Google Scholar : PubMed/NCBI | |
Munksgaard Persson M, Johansson ME, Monsef N, Planck M, Beckman S, Seckl MJ, Rönnstrand L, Påhlman S and Pettersson HM: HIF-2α expression is suppressed in SCLC cells, which survive in moderate and severe hypoxia when HIF-1α is repressed. Am J Pathol. 180:494–504. 2012. View Article : Google Scholar : PubMed/NCBI | |
Shneor D, Folberg R, Pe'er J, Honigman A and Frenkel S: Stable knockdown of CREB, HIF-1 and HIF-2 by replication-competent retroviruses abrogates the responses to hypoxia in hepatocellular carcinoma. Cancer Gene Ther. 24:64–74. 2017. View Article : Google Scholar : PubMed/NCBI | |
Westerlund I, Shi Y, Toskas K, Fell SM, Li S, Surova O, Södersten E, Kogner P, Nyman U, Schlisio S and Holmberg J: Combined epigenetic and differentiation-based treatment inhibits neuroblastoma tumor growth and links HIF2α to tumor suppression. Proc Natl Acad Sci USA. 114:E6137–E6146. 2017. View Article : Google Scholar : PubMed/NCBI | |
Imamura T, Kikuchi H, Herraiz MT, Park DY, Mizukami Y, Mino-Kenduson M, Lynch MP, Rueda BR, Benita Y, Xavier RJ and Chung DC: HIF-1alpha and HIF-2alpha have divergent roles in colon cancer. Int J Cancer. 124:763–771. 2009. View Article : Google Scholar : PubMed/NCBI | |
Coliat P, Ramolu L, Jégu J, Gaiddon C, Jung AC and Pencreach E: Constitutive or induced HIF-2 addiction is involved in resistance to Anti-EGFR treatment and radiation therapy in HNSCC. Cancers (Basel). 11:16072019. View Article : Google Scholar | |
Koh MY, Nguyen V, Lemos R Jr, Darnay BG, Kiriakova G, Abdelmelek M, Ho TH, Karam J, Monzon FA, Jonasch E and Powis G: Hypoxia-induced SUMOylation of E3 ligase HAF determines specific activation of HIF2 in clear-cell renal cell carcinoma. Cancer Res. 75:316–329. 2015. View Article : Google Scholar : PubMed/NCBI | |
Chen R, Xu M, Nagati J and Garcia JA: Coordinate regulation of stress signaling and epigenetic events by Acss2 and HIF-2 in cancer cells. PLoS One. 12:e1902412017. View Article : Google Scholar | |
Choudhry H, Albukhari A, Morotti M, Haider S, Moralli D, Smythies J, Schödel J, Green CM, Camps C, Buffa F, et al: Tumor hypoxia induces nuclear paraspeckle formation through HIF-2α dependent transcriptional activation of NEAT1 leading to cancer cell survival. Oncogene. 34:4482–4490. 2015. View Article : Google Scholar : PubMed/NCBI | |
Chen R, Xu M, Nagati JS, Hogg RT, Das A, Gerard RD and Garcia JA: The acetate/ACSS2 switch regulates HIF-2 stress signaling in the tumor cell microenvironment. PLoS One. 10:e1165152015. | |
Wu XH, Qian C and Yuan K: Correlations of hypoxia-inducible factor-1α/hypoxia-inducible factor-2α expression with angiogenesis factors expression and prognosis in non-small cell lung cancer. Chin Med J (Engl). 124:11–18. 2011.PubMed/NCBI | |
Niu Y, Bao L, Chen Y, Wang C, Luo M, Zhang B, Zhou M, Wang JE, Fang YV, Kumar A, et al: HIF2-Induced long noncoding RNA RAB11B-AS1 Promotes hypoxia-mediated angiogenesis and breast cancer metastasis. Cancer Res. 80:964–975. 2020. View Article : Google Scholar : PubMed/NCBI | |
Sato A, Virgona N, Ando A, Ota M and Yano T: A redox-silent analogue of tocotrienol inhibits cobalt(II) chloride-induced VEGF expression via Yes signaling in mesothelioma cells. Biol Pharm Bull. 37:865–870. 2014. View Article : Google Scholar : PubMed/NCBI | |
Kamai T, Tokura Y, Uematsu T, Sakamoto K, Suzuki I, Takei K, Narimatsu T, Kambara T, Yuki H, Betsunoh H, et al: Elevated serum levels of cardiovascular biomarkers are associated with progression of renal cancer. Open Heart. 5:e0006662018. View Article : Google Scholar : PubMed/NCBI | |
Liu YL, Yu JM, Song XR, Wang XW, Xing LG and Gao BB: Regulation of the chemokine receptor CXCR4 and metastasis by hypoxia-inducible factor in non small cell lung cancer cell lines. Cancer Biol Ther. 5:1320–1326. 2006. View Article : Google Scholar : PubMed/NCBI | |
Giatromanolaki A, Sivridis E, Fiska A and Koukourakis MI: Hypoxia-inducible factor-2 alpha (HIF-2 alpha) induces angiogenesis in breast carcinomas. Appl Immunohistochem Mol Morphol. 14:78–82. 2006. View Article : Google Scholar : PubMed/NCBI | |
Bangoura G, Yang LY, Huang GW and Wang W: Expression of HIF-2alpha/EPAS1 in hepatocellular carcinoma. World J Gastroenterol. 10:525–530. 2004. View Article : Google Scholar : PubMed/NCBI | |
Alam MW, Persson CU, Reinbothe S, Kazi JU, Rönnstrand L, Wigerup C, Ditzel HJ, Lykkesfeldt AE, Påhlman S and Jögi A: HIF2α contributes to antiestrogen resistance via positive bilateral crosstalk with EGFR in breast cancer cells. Oncotarget. 7:11238–11250. 2016. View Article : Google Scholar : PubMed/NCBI | |
Zhao D, Zhai B, He C, Tan G, Jiang X, Pan S, Dong X, Wei Z, Ma L, Qiao H, 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. 26:1030–1039. 2014. View Article : Google Scholar : PubMed/NCBI | |
Moreno Roig E, Groot AJ, Yaromina A, Hendrickx TC, Barbeau LMO, Giuranno L, Dams G, Ient J, Olivo Pimentel V, van Gisbergen MW, et al: HIF-1α and HIF-2α differently regulate the radiation sensitivity of NSCLC cells. Cells. 8:452019. View Article : Google Scholar | |
Koukourakis MI, Bentzen SM, Giatromanolaki A, Wilson GD, Daley FM, Saunders MI, Dische S, Sivridis E and Harris AL: Endogenous markers of two separate hypoxia response pathways (hypoxia inducible factor 2 alpha and carbonic anhydrase 9) are associated with radiotherapy failure in head and neck cancer patients recruited in the CHART randomized trial. J Clin Oncol. 24:727–735. 2006. View Article : Google Scholar : PubMed/NCBI | |
Das B, Pal B, Bhuyan R, Li H, Sarma A, Gayan S, Talukdar J, Sandhya S, Bhuyan S, Gogoi G, et al: MYC Regulates the HIF2α stemness pathway via Nanog and Sox2 to maintain self-renewal in cancer stem cells. versus Non-stem cancer cells. Cancer Res. 79:4015–4025. 2019. View Article : Google Scholar : PubMed/NCBI | |
Hou J, Zhang H, Liu J, Zhao Z, Wang J, Lu Z, Hu B, Zhou J, Zhao Z, Feng M, et al: YTHDF2 reduction fuels inflammation and vascular abnormalization in hepatocellular carcinoma. Mol Cancer. 18:1632019. View Article : Google Scholar : PubMed/NCBI | |
Zhao CX, Luo CL and Wu XH: Hypoxia promotes 786-O cells invasiveness and resistance to sorafenib via HIF-2α/COX-2. Med Oncol. 32:4192015. View Article : Google Scholar : PubMed/NCBI | |
Vukovic M, Guitart AV, Sepulveda C, Villacreces A, O'Duibhir E, Panagopoulou TI, Ivens A, Menendez-Gonzalez J, Iglesias JM, Allen L, et al: Hif-1α and Hif-2α synergize to suppress AML development but are dispensable for disease maintenance. J Exp Med. 212:2223–2234. 2015. View Article : Google Scholar : PubMed/NCBI | |
Jiang L, Shi S, Shi Q, Zhang H, Xia Y and Zhong T: MicroRNA-519d-3p inhibits proliferation and promotes apoptosis by targeting HIF-2α in cervical cancer under hypoxic conditions. Oncol Res. 26:1055–1062. 2018. View Article : Google Scholar : PubMed/NCBI | |
Pangou E, Befani C, Mylonis I, Samiotaki M, Panayotou G, Simos G and Liakos P: HIF-2α phosphorylation by CK1δ promotes erythropoietin secretion in liver cancer cells under hypoxia. J Cell Sci. 129:4213–4226. 2016. View Article : Google Scholar : PubMed/NCBI | |
Liu N, Luo J, Kuang D, Xu S, Duan Y, Xia Y, Wei Z, Xie X, Yin B, Chen F, et al: Lactate inhibits ATP6V0d2 expression in tumor-associated macrophages to promote HIF-2α-mediated tumor progression. J Clin Invest. 129:631–646. 2019. View Article : Google Scholar : PubMed/NCBI | |
Wang Z, Wei Y, Zhang R, Su L, Gogarten SM, Liu G, Brennan P, Field JK, McKay JD, Lissowska J, et al: Multi-Omics analysis reveals a HIF network and hub gene EPAS1 associated with lung adenocarcinoma. Ebiomedicine. 32:93–101. 2018. View Article : Google Scholar : PubMed/NCBI | |
Luan Y, Gao C, Miao Y, Li Y, Wang Z and Qiu X: Clinicopathological and prognostic significance of HIF-1alpha and HIF-2alpha expression in small cell lung cancer. Pathol Res Pract. 209:184–189. 2013. View Article : Google Scholar : PubMed/NCBI | |
Yu S, Ren H, Li Y, Liang X, Ning Q, Chen X, Chen M and Hu T: HOXA4-dependent transcriptional activation of AXL promotes cisplatin-resistance in lung adenocarcinoma cells. Anticancer Agents Med Chem. 18:2062–2067. 2018. View Article : Google Scholar : PubMed/NCBI | |
Iwamoto S, Tanimoto K, Nishio Y, Putra AC, Fuchita H, Ohe M, Sutani A, Kuraki T, Hiyama K, Murakami I, et al: Association of EPAS1 gene rs4953354 polymorphism with susceptibility to lung adenocarcinoma in female Japanese non-smokers. J Thorac Oncol. 9:1709–1713. 2014. View Article : Google Scholar : PubMed/NCBI | |
Sárosi V, Balikó Z, Smuk G, László T, Szabó M, Ruzsics I and Mezősi E: The frequency of EGFR mutation in lung adenocarcinoma and the efficacy of tyrosine kinase inhibitor therapy in a hungarian cohort of patients. Pathol Oncol Res. 22:755–761. 2016. View Article : Google Scholar : PubMed/NCBI | |
Gao ZJ, Wang Y, Yuan WD, Yuan JQ and Yuan K: HIF-2α not HIF-1α overexpression confers poor prognosis in non-small cell lung cancer. Tumour Biol. 39:10104283177096372017. View Article : Google Scholar : PubMed/NCBI | |
Xu Y, Zhao Y, Xu W, Luo F, Wang B, Li Y, Pang Y and Liu Q: Involvement of HIF-2α-mediated inflammation in arsenite-induced transformation of human bronchial epithelial cells. Toxicol Appl Pharmacol. 272:542–550. 2013. View Article : Google Scholar : PubMed/NCBI | |
Pang Y, Xu Y, Li H, Li Y, Zhao Y, Jiang R, Shen L, Zhou J, Wang X and Liu Q: The inhibition of HIF-2α on the ATM/Chk-2 pathway is involved in the promotion effect of arsenite on benzo(a)pyrene-induced cell transformation. Toxicol Lett. 218:105–117. 2013. View Article : Google Scholar : PubMed/NCBI | |
Zhou Q, Chen T, Ibe JC, Raj JU and Zhou G: Loss of either hypoxia inducible factor 1 or 2 promotes lung cancer cell colonization. Cell Cycle. 10:2233–2234. 2011. View Article : Google Scholar : PubMed/NCBI | |
Kamlah F, Eul BG, Li S, Lang N, Marsh LM, Seeger W, Grimminger F, Rose F and Hänze J: Intravenous injection of siRNA directed against hypoxia-inducible factors prolongs survival in a Lewis lung carcinoma cancer model. Cancer Gene Ther. 16:195–205. 2009. View Article : Google Scholar : PubMed/NCBI | |
Yuan S, Xiang Y, Wang G, Zhou M, Meng G, Liu Q, Hu Z, Li C, Xie W, Wu N, et al: Hypoxia-sensitive LINC01436 is regulated by E2F6 and acts as an oncogene by targeting miR-30a-3p in non-small cell lung cancer. Mol Oncol. 13:840–856. 2019. View Article : Google Scholar : PubMed/NCBI | |
Martinengo C, Poggio T, Menotti M, Scalzo MS, Mastini C, Ambrogio C, Pellegrino E, Riera L, Piva R, Ribatti D, et al: ALK-dependent control of hypoxia-inducible factors mediates tumor growth and metastasis. Cancer Res. 74:6094–6106. 2014. View Article : Google Scholar : PubMed/NCBI | |
Hong CF, Chen WY and Wu CW: Upregulation of Wnt signaling under hypoxia promotes lung cancer progression. Oncol Rep. 38:1706–1714. 2017. View Article : Google Scholar : PubMed/NCBI | |
Mazumdar J, Hickey MM, Pant DK, Durham AC, Sweet-Cordero A, Vachani A, Jacks T, Chodosh LA, Kissil JL, Simon MC and Keith B: HIF-2alpha deletion promotes Kras-driven lung tumor development. Proc Natl Acad Sci USA. 107:14182–14187. 2010. View Article : Google Scholar : PubMed/NCBI | |
Wang X, Cao P, Li Z, Wu D, Wang X and Liang G: EPAS-1 mediates SP-1-dependent FBI-1 expression and regulates tumor cell survival and proliferation. Int J Mol Sci. 15:15689–15699. 2014. View Article : Google Scholar : PubMed/NCBI | |
Higashi K, Yamagishi T, Ueda Y, Ishigaki Y, Shimasaki M, Nakamura Y, Oguchi M, Takegami T, Sagawa M and Tonami H: Correlation of HIF-1α/HIF-2α expression with FDG uptake in lung adenocarcinoma. Ann Nucl Med. 30:708–715. 2016. View Article : Google Scholar : PubMed/NCBI | |
Yu L and Hales CA: Long-term exposure to hypoxia inhibits tumor progression of lung cancer in rats and mice. BMC Cancer. 11:3312011. View Article : Google Scholar : PubMed/NCBI | |
Kim WY, Perera S, Zhou B, Carretero J, Yeh JJ, Heathcote SA, Jackson AL, Nikolinakos P, Ospina B, Naumov G, et al: HIF2alpha cooperates with RAS to promote lung tumorigenesis in mice. J Clin Invest. 119:2160–2170. 2009. View Article : Google Scholar : PubMed/NCBI | |
Shao JS, Sun J, Wang S, Chung K, Du JT, Wang J, Qiu XS, Wang EH and Wu GP: HPV16 E6/E7 upregulates HIF-2α and VEGF by inhibiting LKB1 in lung cancer cells. Tumour Biol. 39:10104283177171372017. View Article : Google Scholar : PubMed/NCBI | |
Karoor V, Le M, Merrick D, Fagan KA, Dempsey EC and Miller YE: Alveolar hypoxia promotes murine lung tumor growth through a VEGFR-2/EGFR-dependent mechanism. Cancer Prev Res (Phila). 5:1061–1071. 2012. View Article : Google Scholar : PubMed/NCBI | |
Giatromanolaki A, Koukourakis MI, Sivridis E, Turley H, Talks K, Pezzella F, Gatter KC and Harris AL: Relation of hypoxia inducible factor 1 alpha and 2 alpha in operable non-small cell lung cancer to angiogenic/molecular profile of tumours and survival. Br J Cancer. 85:881–890. 2001. View Article : Google Scholar : PubMed/NCBI | |
Pullamsetti SS, Banat GA, Schmall A, Szibor M, Pomagruk D, Hänze J, Kolosionek E, Wilhelm J, Braun T, Grimminger F, et al: Phosphodiesterase-4 promotes proliferation and angiogenesis of lung cancer by crosstalk with HIF. Oncogene. 32:1121–1134. 2013. View Article : Google Scholar : PubMed/NCBI | |
Zhen Q, Zhang Y, Gao L, Wang R, Chu W, Zhao X, Li Z, Li H, Zhang B, Lv B and Liu J: EPAS1 promotes peritoneal carcinomatosis of non-small-cell lung cancer by enhancing mesothelial-mesenchymal transition. Strahlenther Onkol. 197:141–149. 2021. View Article : Google Scholar : PubMed/NCBI | |
Chan SM, Lin BF, Wong CS, Chuang WT, Chou YT and Wu ZF: Levobuipivacaine-Induced Dissemination of A549 lung cancer cells. Sci Rep. 7:86462017. View Article : Google Scholar : PubMed/NCBI | |
Shaikh D, Zhou Q, Chen T, Ibe JC, Raj JU and Zhou G: cAMP-dependent protein kinase is essential for hypoxia-mediated epithelial-mesenchymal transition, migration, and invasion in lung cancer cells. Cell Signal. 24:2396–2406. 2012. View Article : Google Scholar : PubMed/NCBI | |
Lin SC, Chung CH, Chung CH, Kuo MH, Hsieh CH, Chiu YF, Shieh YS, Chou YT and Wu CW: OCT4B mediates hypoxia-induced cancer dissemination. Oncogene. 38:1093–1105. 2019. View Article : Google Scholar : PubMed/NCBI | |
Jia R, Liang Y, Chen R, Liu G, Wang H, Tang M, Zhou X, Wang H, Yang Y, Wei H, et al: Osteopontin facilitates tumor metastasis by regulating epithelial-mesenchymal plasticity. Cell Death Dis. 7:e25642016. View Article : Google Scholar : PubMed/NCBI | |
Zhou R, Zhou X, Yin Z, Guo J, Hu T, Jiang S, Liu L, Dong X, Zhang S and Wu G: Tumor invasion and metastasis regulated by microRNA-184 and microRNA-574-5p in small-cell lung cancer. Oncotarget. 6:44609–44622. 2015. View Article : Google Scholar : PubMed/NCBI | |
Li Y, Qiu X, Zhang S, Zhang Q and Wang E: Hypoxia induced CCR7 expression via HIF-1alpha and HIF-2alpha correlates with migration and invasion in lung cancer cells. Cancer Biol Ther. 8:322–330. 2009. View Article : Google Scholar : PubMed/NCBI | |
Gao ZJ, Yuan WD, Yuan JQ, Yuan K and Wang Y: Downregulation of HIF-2α reverse the chemotherapy resistance of lung adenocarcinoma A549 cells to Cisplatin. Med Sci Monit. 24:1104–1111. 2018. View Article : Google Scholar : PubMed/NCBI | |
Stoleriu MG, Steger V, Mustafi M, Michaelis M, Cinatl J, Schneider W, Nolte A, Kurz J, Wendel HP, Schlensak C and Walker T: A new strategy in the treatment of chemoresistant lung adenocarcinoma via specific siRNA transfection of SRF, E2F1, Survivin, HIF and STAT3. Eur J Cardiothorac Surg. 46:877–886. 2014. View Article : Google Scholar : PubMed/NCBI | |
Moreno Roig E, Groot AJ, Yaromina A, Hendrickx TC, Barbeau LMO, Giuranno L, Dams G, Ient J, Olivo Pimentel V, van Gisbergen MW, et al: HIF-1α and HIF-2α differently regulate the radiation sensitivity of NSCLC Cells. Cells. 8:452019. View Article : Google Scholar | |
Sun JC, He F, Yi W, Wan MH, Li R, Wei X, Wu R and Niu DL: High expression of HIF-2α and its anti-radiotherapy effect in lung cancer stem cells. Genet Mol Res. 14:18110–18120. 2015. View Article : Google Scholar : PubMed/NCBI | |
Zhen Q, Liu JF, Liu JB, Wang RF, Chu WW, Zhang YX, Tan GL, Zhao XJ and Lv BL: Endothelial PAS domain-containing protein 1 confers TKI-resistance by mediating EGFR and MET pathways in non-small cell lung cancer cells. Cancer Biol Ther. 16:549–557. 2015. View Article : Google Scholar : PubMed/NCBI | |
Hajizadeh F, Okoye I, Esmaily M, Ghasemi Chaleshtari M, Masjedi A, Azizi G, Irandoust M, Ghalamfarsa G and Jadidi-Niaragh F: Hypoxia inducible factors in the tumor microenvironment as therapeutic targets of cancer stem cells. Life Sci. 237:1169522019. View Article : Google Scholar : PubMed/NCBI | |
Ye XQ, Li Q, Wang GH, Sun FF, Huang GJ, Bian XW, Yu SC and Qian GS: Mitochondrial and energy metabolism-related properties as novel indicators of lung cancer stem cells. Int J Cancer. 129:820–831. 2011. View Article : Google Scholar : PubMed/NCBI | |
Gao Y, Feng J, Wu L, Zhan S and Sun J: Expression and pathological mechanism of MMP-9 and HIF-2α in CD133(+) lung cancer stem cells. Zhonghua Yi Xue Za Zhi. 95:2607–2611. 2015.(In Chinese). PubMed/NCBI | |
Wei-Hua W, Ning Z, Qian C and Dao-Wen J: ZIC2 promotes cancer stem cell traits via up-regulating OCT4 expression in lung adenocarcinoma cells. J Cancer. 11:6070–6080. 2020. View Article : Google Scholar : PubMed/NCBI | |
Zhang X, Hu F, Li C, Zheng X, Zhang B, Wang H, Tao G, Xu J, Zhang Y and Han B: OCT4&SOX2-specific cytotoxic T lymphocytes plus programmed cell death protein 1 inhibitor presented with synergistic effect on killing lung cancer stem-like cells in vitro and treating drug-resistant lung cancer mice in vivo. J Cell Physiol. 234:6758–6768. 2019. View Article : Google Scholar : PubMed/NCBI | |
Zhang X, Zhang Y, Xu J, Wang H, Zheng X, Lou Y and Han B: Antigen presentation of the Oct4 and Sox2 peptides by CD154-activated B lymphocytes enhances the killing effect of cytotoxic T lymphocytes on tumor stem-like cells derived from cisplatin-resistant lung cancer cells. J Cancer. 9:367–374. 2018. View Article : Google Scholar : PubMed/NCBI | |
Phiboonchaiyanan PP and Chanvorachote P: Suppression of a cancer stem-like phenotype mediated by alpha-lipoic acid in human lung cancer cells through down-regulation of β-catenin and Oct-4. Cell Oncol (Dordr). 40:497–510. 2017. View Article : Google Scholar : PubMed/NCBI | |
Kobayashi I, Takahashi F, Nurwidya F, Nara T, Hashimoto M, Murakami A, Yagishita S, Tajima K, Hidayat M, Shimada N, et al: Oct4 plays a crucial role in the maintenance of gefitinib-resistant lung cancer stem cells. Biochem Biophys Res Commun. 473:125–132. 2016. View Article : Google Scholar : PubMed/NCBI | |
Xu Y, Li Y, Pang Y, Ling M, Shen L, Yang X, Zhang J, Zhou J, Wang X and Liu Q: EMT and stem cell-like properties associated with HIF-2α are involved in arsenite-induced transformation of human bronchial epithelial cells. PLoS One. 7:e377652012. View Article : Google Scholar : PubMed/NCBI | |
Wang R, Sun Q, Wang P, Liu M, Xiong S, Luo J, Huang H, Du Q, Geller DA and Cheng B: Notch and Wnt/β-catenin signaling pathway play important roles in activating liver cancer stem cells. Oncotarget. 7:5754–5768. 2016. View Article : Google Scholar : PubMed/NCBI | |
Zhu JY, Yang X, Chen Y, Jiang Y, Wang SJ, Li Y, Wang XQ, Meng Y, Zhu MM, Ma X, et al: Curcumin suppresses lung cancer stem cells via inhibiting Wnt/β-catenin and Sonic Hedgehog Pathways. Phytother Res. 31:680–688. 2017. View Article : Google Scholar : PubMed/NCBI | |
Li C, Lu HJ, Na FF, Deng L, Xue JX, Wang JW, Wang YQ, Li QL and Lu Y: Prognostic role of hypoxic inducible factor expression in non-small cell lung cancer: A meta-analysis. Asian Pac J Cancer Prev. 14:3607–3612. 2013. View Article : Google Scholar : PubMed/NCBI | |
Putra AC, Eguchi H, Lee KL, Yamane Y, Gustine E, Isobe T, Nishiyama M, Hiyama K, Poellinger L and Tanimoto K: The A Allele at rs13419896 of EPAS1 is associated with enhanced expression and poor prognosis for non-small cell lung cancer. PLoS One. 10:e01344962015. View Article : Google Scholar : PubMed/NCBI | |
de Haas S, Delmar P, Bansal AT, Moisse M, Miles DW, Leighl N, Escudier B, Van Cutsem E, Carmeliet P, Scherer SJ, et al: Genetic variability of VEGF pathway genes in six randomized phase III trials assessing the addition of bevacizumab to standard therapy. Angiogenesis. 17:909–920. 2014. View Article : Google Scholar : PubMed/NCBI | |
Ma H, Liu B, Wang S and Liu J: MicroRNA-383 is a tumor suppressor in human lung cancer by targeting endothelial PAS domain-containing protein 1. Cell Biochem Funct. 34:613–619. 2016. View Article : Google Scholar : PubMed/NCBI | |
Sato M, Tanaka T, Maeno T, Sando Y, Suga T, Maeno Y, Sato H, Nagai R and Kurabayashi M: Inducible expression of endothelial PAS domain protein-1 by hypoxia in human lung adenocarcinoma A549 cells. Role of Src family kinases-dependent pathway. Am J Respir Cell Mol Biol. 26:127–134. 2002. View Article : Google Scholar : PubMed/NCBI |