Non-canonical HIF-2α function drives autonomous breast cancer cell growth via an AREG-EGFR/ErbB4 autocrine loop

Oncogene

Volumn 31, Issue 18, 2012, Pages 2283-2297

  Stiehl, D P ^a   Bordoli, M R ^a,f   Abreu Rodriguez I ^a   Wollenick, K ^a   Schraml, P ^b   Gradin, K ^c   Poellinger, L ^c,d   Kristiansen, G ^e   Wenger, R H ^a  

^a UNIVERSITY OF ZURICH   (Switzerland)

^b UNIVERSITY HOSPITAL ZURICH   (Switzerland)

^c KAROLINSKA INSTITUTE   (Sweden)

^d NATIONAL UNIVERSITY OF SINGAPORE   (Singapore)

^e UNIVERSITY HOSPITAL BONN   (Germany)

^f HARVARD SCHOOL OF DENTAL MEDICINE   (United States)

Author keywords

EGF signaling; growth factors; HIF target genes; hypoxic expression profiles; luminal breast cancer

Indexed keywords

AMPHIREGULIN; BETA ACTIN; CARBONATE DEHYDRATASE IX; CYTOKERATIN 5; EPIDERMAL GROWTH FACTOR RECEPTOR; EPIDERMAL GROWTH FACTOR RECEPTOR 2; EPIDERMAL GROWTH FACTOR RECEPTOR 3; EPIDERMAL GROWTH FACTOR RECEPTOR 4; ESTROGEN RECEPTOR; GLUCOSE TRANSPORTER 1; HYPOXIA INDUCIBLE FACTOR 1ALPHA; HYPOXIA INDUCIBLE FACTOR 2ALPHA; INOSITOL 1,4,5 TRISPHOSPHATE RECEPTOR; OXYGENASE; PLASMINOGEN ACTIVATOR INHIBITOR 1; PROGESTERONE RECEPTOR; PROTEIN PHD2; PROTEIN PHD3; PROTEIN REDD1; PROTEIN WISP2; REGULATOR PROTEIN; SHORT HAIRPIN RNA; UNCLASSIFIED DRUG; WNT PROTEIN;

AREG GENE; ARTICLE; AUTOCRINE EFFECT; BREAST CANCER; BREAST CARCINOGENESIS; CA9 GENE; CANCER CELL; CANCER GROWTH; CANCER PATIENT; CANCER SURVIVAL; CONTROLLED STUDY; DOWN REGULATION; EGFR GENE; ERBB3 GENE; ERBB4 GENE; FEMALE; GENE CONTROL; GENETIC TRANSCRIPTION; GLUT1 GENE; HIF 2ALPHA GENE; HUMAN; HUMAN CELL; HUMAN TISSUE; HYPOXEMIA; IN VITRO STUDY; ONCOGENE; PAI1 GENE; PHENOTYPE; PRIORITY JOURNAL; PROGNOSIS; PROMOTER REGION; PROTEIN DNA BINDING; PROTEIN EXPRESSION; PROTEIN FAMILY; PROTEIN MOTIF; RECEPTOR UPREGULATION; RNA INTERFERENCE; SIGNAL TRANSDUCTION; SOLID TUMOR; TISSUE MICROARRAY; TUMOR DIFFERENTIATION; TUMOR MICROENVIRONMENT; WISP2 GENE;

AUTOCRINE COMMUNICATION; BASIC HELIX-LOOP-HELIX TRANSCRIPTION FACTORS; BREAST NEOPLASMS; CCN INTERCELLULAR SIGNALING PROTEINS; CELL HYPOXIA; CELL LINE, TUMOR; CELL PROLIFERATION; DISEASE-FREE SURVIVAL; EPIDERMAL GROWTH FACTOR; FEMALE; GLYCOPROTEINS; HUMANS; INTERCELLULAR SIGNALING PEPTIDES AND PROTEINS; RECEPTOR, EPIDERMAL GROWTH FACTOR; REPRESSOR PROTEINS; SIGNAL TRANSDUCTION;

EID: 84861339790     PISSN: 09509232     EISSN: 14765594     Source Type: Journal    
DOI: 10.1038/onc.2011.417     Document Type: Article

References (52)

1. Aprelikova O, Wood M, Tackett S, Chandramouli GV, Barrett JC. (2006). Role of ETS transcription factors in the hypoxia-inducible factor-2 target gene selection. Cancer Res 66: 5641-5647. (Pubitemid 43927116)
2. Banerjee S, Dhar G, Haque I, Kambhampati S, Mehta S, Sengupta K ,et al. (2008). CCN5/WISP-2 expression in breast adenocarcinoma is associated with less frequent progression of the disease and suppresses the invasive phenotypes of tumor cells. Cancer Res 68: 7606-7612.
3. Bertout JA, Patel SA, Simon MC. (2008). The impact of O2 availability on human cancer. Nat Rev Cancer 8: 967-975.
4. Bordoli MR, Stiehl DP, Borsig L, Kristiansen G, Hausladen S, Schraml P ,et al. (2011). Prolyl-4-hydroxylase PHD2-and hypoxiainducible factor 2-dependent regulation of amphiregulin contributes to breast tumorigenesis. Oncogene 30: 548-560.
5. Brugarolas J, Lei K, Hurley RL, Manning BD, Reiling JH, Hafen E ,et al. (2004). Regulation of mTOR function in response to hypoxia by REDD1 and the TSC1/TSC2 tumor suppressor complex. Genes Dev 18: 2893-2904. (Pubitemid 39602308)
6. Covello KL, Kehler J, Yu H, Gordan JD, Arsham AM, Hu CJ ,et al. (2006). HIF-2alpha regulates Oct-4: effects of hypoxia on stem cell function, embryonic development, and tumor growth. Genes Dev 20: 557-570. (Pubitemid 43345322)
7. Cummins EP, Taylor CT. (2005). Hypoxia-responsive transcription factors. Pflugers Arch 450: 363-371. (Pubitemid 41380694)
8. Dewhirst MW, Cao Y, Moeller B. (2008). Cycling hypoxia and free radicals regulate angiogenesis and radiotherapy response. Nat Rev Cancer 8: 425-437. (Pubitemid 351744964)
9. Elvert G, Kappel A, Heidenreich R, Englmeier U, Lanz S, Acker T ,et al. (2003). Cooperative interaction of hypoxia-inducible factor-2alpha (HIF-2alpha) and Ets-1 in the transcriptional activation of vascular endothelial growth factor receptor-2 (Flk-1). J Biol Chem 278: 7520-7530. (Pubitemid 36800759)
10. Elvidge GP, Glenny L, Appelhoff RJ, Ratcliffe PJ, Ragoussis J, Gleadle JM. (2006). Concordant regulation of gene expression by hypoxia and 2-oxoglutarate-dependent dioxygenase inhibition: the role of HIF-1alpha, HIF-2alpha, and other pathways. J Biol Chem 281: 15215-15226. (Pubitemid 43855111)
11. Franovic A, Holterman CE, Payette J, Lee S. (2009). Human cancers converge at the HIF-2alpha oncogenic axis. Proc Natl Acad Sci USA 106: 21306-21311.
12. Fritah A, Saucier C, De Wever O, Bracke M, Bieche I, Lidereau R ,et al. (2008). Role of WISP-2/CCN5 in the maintenance of a differentiated and noninvasive phenotype in human breast cancer cells. Mol Cell Biol 28: 1114-1123. (Pubitemid 351160067)
13. Gatenby RA, Silva AS, Gillies RJ, Frieden BR. (2009). Adaptive therapy. Cancer Res 69: 4894-4903.
14. Gatenby RA, Smallbone K, Maini PK, Rose F, Averill J, Nagle RB ,et al. (2007). Cellular adaptations to hypoxia and acidosis during somatic evolution of breast cancer. Br J Cancer 97: 646-653. (Pubitemid 47339892)
15. Gordan JD, Bertout JA, Hu CJ, Diehl JA, Simon MC. (2007). HIF-2alpha promotes hypoxic cell proliferation by enhancing c-myc transcriptional activity. Cancer Cell 11: 335-347. (Pubitemid 46518312)
16. Gordan JD, Lal P, Dondeti VR, Letrero R, Parekh KN, Oquendo CE ,et al. (2008). HIF-alpha effects on c-Myc distinguish two subtypes of sporadic VHL-deficient clear cell renal carcinoma. Cancer Cell 14: 435-446.
17. Helczynska K, Larsson AM, Holmquist Mengelbier L, Bridges E, Fredlund E, Borgquist S ,et al. (2008). Hypoxia-inducible factor-2alpha correlates to distant recurrence and poor outcome in invasive breast cancer. Cancer Res 68: 9212-9220.
18. Holmquist-Mengelbier L, Fredlund E, Lofstedt T, Noguera R, Navarro S, Nilsson H ,et al. (2006). Recruitment of HIF-1alpha and HIF-2alpha to common target genes is differentially regulated in neuroblastoma: HIF-2alpha promotes an aggressive phenotype. Cancer Cell 10: 413-423. (Pubitemid 44693470)
19. Hu CJ, Sataur A, Wang L, Chen H, Simon MC. (2007). The N-terminal transactivation domain confers target gene specificity of hypoxia-inducible factors HIF-1alpha and HIF-2alpha. Mol Biol Cell 18: 4528-4542. (Pubitemid 350060179)
20. Hu CJ, Wang LY, Chodosh LA, Keith B, Simon MC. (2003). Differential roles of hypoxia-inducible factor 1a (HIF-1a) and HIF-2a in hypoxic gene regulation. Mol Cell Biol 23: 9361-9374. (Pubitemid 37499822)
21. Iyer NV, Kotch LE, Agani F, Leung SW, Laughner E, Wenger RH ,et al. (1998). Cellular and developmental control of O2 homeostasis by hypoxia-inducible factor 1a. Genes Dev 12: 149-162. (Pubitemid 28060446)
22. Kao J, Salari K, Bocanegra M, Choi YL, Girard L, Gandhi J ,et al. (2009). Molecular profiling of breast cancer cell lines defines relevant tumor models and provides a resource for cancer gene discovery. PLoS One 4: e6146.
23. Kim HS, Kim MS, Hancock AL, Harper JC, Park JY, Poy G ,et al. (2007). Identification of novel Wilms' tumor suppressor gene target genes implicated in kidney development. J Biol Chem 282: 16278-16287. (Pubitemid 47100403)
24. Kim WY, Perera S, Zhou B, Carretero J, Yeh JJ, Heathcote SA ,et al. (2009). HIF2alpha cooperates with RAS to promote lung tumorigenesis in mice. J Clin Invest 119: 2160-2170.
25. Lau KW, Tian YM, Raval RR, Ratcliffe PJ, Pugh CW. (2007). Target gene selectivity of hypoxia-inducible factor-alpha in renal cancer cells is conveyed by post-DNA-binding mechanisms. Br J Cancer 96: 1284-1292. (Pubitemid 46625064)
26. Le Bras A, Lionneton F, Mattot V, Lelievre E, Caetano B, Spruyt N ,et al. (2007). HIF-2alpha specifically activates the VE-cadherin promoter independently of hypoxia and in synergy with Ets-1 through two essential ETS-binding sites. Oncogene 26: 7480-7489. (Pubitemid 350158718)
27. Lee SB, Huang K, Palmer R, Truong VB, Herzlinger D, Kolquist KA ,et al. (1999). The Wilms tumor suppressor WT1 encodes a transcriptional activator of amphiregulin. Cell 98: 663-673. (Pubitemid 29418957)
28. Lehmann S, Stiehl DP, Honer M, Dominietto M, Keist R, Kotevic I ,et al. (2009). Longitudinal and multimodal in vivo imaging of tumor hypoxia and its downstream molecular events. Proc Natl Acad Sci USA 106: 14004-14009.
29. Liao D, Corle C, Seagroves TN, Johnson RS. (2007). Hypoxiainducible factor-1alpha is a key regulator of metastasis in a transgenic model of cancer initiation and progression. Cancer Res 67: 563-572. (Pubitemid 46192193)
30. Loeb DM, Evron E, Patel CB, Sharma PM, Niranjan B, Buluwela L ,et al. (2001). Wilms' tumor suppressor gene (WT1) is expressed in primary breast tumors despite tumor-specific promoter methylation. Cancer Res 61: 921-925. (Pubitemid 32174404)
31. Mazumdar J, Hickey MM, Pant DK, Durham AC, Sweet-Cordero A, Vachani A ,et al. (2010). HIF-2alpha deletion promotes Krasdriven lung tumor development. Proc Natl Acad Sci USA 107: 14182-14187.
32. Minamishima YA, Moslehi J, Padera RF, Bronson RT, Liao R, Kaelin Jr WG. (2009). A feedback loop involving the Phd3 prolyl hydroxylase tunes the mammalian hypoxic response in vivo. Mol Cell Biol 29: 5729-5741.
33. Mole DR, Blancher C, Copley RR, Pollard PJ, Gleadle JM, Ragoussis J ,et al. (2009). Genome-wide association of hypoxiainducible factor (HIF)-1alpha and HIF-2alpha DNA binding with expression profiling of hypoxia-inducible transcripts. J Biol Chem 284: 16767-16775.
34. Neve RM, Chin K, Fridlyand J, Yeh J, Baehner FL, Fevr T ,et al. (2006). A collection of breast cancer cell lines for the study of functionally distinct cancer subtypes. Cancer Cell 10: 515-527. (Pubitemid 44854747)
35. Nielsen TO, Hsu FD, Jensen K, Cheang M, Karaca G, Hu Z ,et al. (2004). Immunohistochemical and clinical characterization of the basal-like subtype of invasive breast carcinoma. Clin Cancer Res 10: 5367-5374. (Pubitemid 39100473)
36. Park SK, Dadak AM, Haase VH, Fontana L, Giaccia AJ, Johnson RS. (2003). Hypoxia-induced gene expression occurs solely through the action of hypoxia-inducible factor 1alpha (HIF-1alpha): role of cytoplasmic trapping of HIF-2alpha. Mol Cell Biol 23: 4959-4971. (Pubitemid 36793341)
37. Patel SA, Simon MC. (2008). Biology of hypoxia-inducible factor-2alpha in development and disease. Cell Death Differ 15: 628-634. (Pubitemid 351405065)
38. Perou CM, Sorlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA ,et al. (2000). Molecular portraits of human breast tumours. Nature 406: 747-752.
39. Raval RR, Lau KW, Tran MG, Sowter HM, Mandriota SJ, Li JL ,et al. (2005). Contrasting properties of hypoxia-inducible factor 1 (HIF-1) and HIF-2 in von Hippel-Lindau-associated renal cell carcinoma. Mol Cell Biol 25: 5675-5686. (Pubitemid 40853601)
40. Saito T, Fukai A, Mabuchi A, Ikeda T, Yano F, Ohba S ,et al. (2010). Transcriptional regulation of endochondral ossification by HIF-2alpha during skeletal growth and osteoarthritis development. Nat Med 16: 678-686.
41. Semenza GL. (2010). Defining the role of hypoxia-inducible factor 1 in cancer biology and therapeutics. Oncogene 29: 625-634.
42. Semenza GL, Roth PH, Fang HM, Wang GL. (1994). Transcriptional regulation of genes encoding glycolytic enzymes by hypoxiainducible factor 1. J Biol Chem 269: 23757-23763. (Pubitemid 24293585)
43. Sowter HM, Raval RR, Moore JW, Ratcliffe PJ, Harris AL. (2003). Predominant role of hypoxia-inducible transcription factor (Hif)-1alpha versus Hif-2alpha in regulation of the transcriptional response to hypoxia. Cancer Res 63: 6130-6134. (Pubitemid 37255150)
44. Stiehl DP, Wirthner R, Koditz J, Spielmann P, Camenisch G, Wenger RH. (2006). Increased prolyl 4-hydroxylase domain proteins compensate for decreased oxygen levels. Evidence for an autoregulatory oxygen-sensing system. J Biol Chem 281: 23482-23491. (Pubitemid 44274123)
45. Tomes L, Emberley E, Niu Y, Troup S, Pastorek J, Strange K ,et al. (2003). Necrosis and hypoxia in invasive breast carcinoma. Breast Cancer Res Treat 81: 61-69. (Pubitemid 37108441)
46. Wang V, Davis DA, Veeranna RP, Haque M, Yarchoan R. (2010). Characterization of the activation of protein tyrosine phosphatase, receptor-type, Z polypeptide 1 (PTPRZ1) by hypoxia inducible factor-2 alpha. PLoS One 5: e9641.
47. Wenger RH, Stiehl DP, Camenisch G. (2005). Integration of oxygen signaling at the consensus HRE. Sci STKE 2005: re12.
48. Wykoff CC, Beasley NJ, Watson PH, Turner KJ, Pastorek J, Sibtain A ,et al. (2000). Hypoxia-inducible expression of tumor-associated carbonic anhydrases. Cancer Res 60: 7075-7083. (Pubitemid 32059187)
49. Yamashita T, Ohneda K, Nagano M, Miyoshi C, Kaneko N, Miwa Y ,et al. (2008). Hypoxia-inducible transcription factor-2alpha in endothelial cells regulates tumor neovascularization through activation of ephrin A1. J Biol Chem 283: 18926-18936.
50. Yan Q, Bartz S, Mao M, Li L, Kaelin Jr WG. (2007). The hypoxiainducible factor 2alpha N-terminal and C-terminal transactivation domains cooperate to promote renal tumorigenesis in vivo. Mol Cell Biol 27: 2092-2102. (Pubitemid 46418467)
51. Yang S, Kim J, Ryu JH, Oh H, Chun CH, Kim BJ ,et al. (2010). Hypoxia-inducible factor-2alpha is a catabolic regulator of osteoarthritic cartilage destruction. Nat Med 16: 687-693.
52. Yu P, Kodadek T. (2007). Dynamics of the hypoxia-inducible factor-1-vascular endothelial growth factor promoter complex. J Biol Chem 282: 35035-35045. (Pubitemid 350232415)