Role of hypoxia in the hallmarks of human cancer

Journal of Cellular Biochemistry

Volumn 107, Issue 6, 2009, Pages 1053-1062

  Ruan, Kai ^a   Song, Gang ^a   Ouyang, Gaoliang ^a  

^a XIAMEN UNIVERSITY   (China)

Author keywords

Cancer; Hypoxia; Hypoxia inducible factor; Metabolism; Metastasis; Microenvironment

Indexed keywords

EPIDERMAL GROWTH FACTOR RECEPTOR; HYPOXIA INDUCIBLE FACTOR 1; MITOGEN ACTIVATED PROTEIN KINASE 1; PLATELET DERIVED GROWTH FACTOR; SOMATOMEDIN B; SOMATOMEDIN C; VASCULOTROPIN; VASCULOTROPIN RECEPTOR 1;

ANGIOGENESIS; APOPTOSIS; CANCER INVASION; CELL HYPOXIA; CELL INVASION; CELL MIGRATION; CELL PROLIFERATION; ENZYME ACTIVATION; GENOMIC INSTABILITY; GLYCOLYSIS; HUMAN; IMMUNE SYSTEM; METASTASIS; NEOPLASM; NONHUMAN; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN EXPRESSION; REVIEW; SIGNAL TRANSDUCTION;

ANOXIA; HUMANS; HYPOXIA-INDUCIBLE FACTOR 1; NEOPLASMS; SIGNAL TRANSDUCTION;

MAMMALIA;

EID: 68049105076     PISSN: 07302312     EISSN: 10974644     Source Type: Journal    
DOI: 10.1002/jcb.22214     Document Type: Review

References (127)

1. Aragones J, Fraisl P, Baes M, Carmeliet P. 2009. Oxygen sensors at the crossroad of metabolism. Cell Metab 9:11-22.
2. Artandi SE, DePinho RA. 2000. A critical role for telomeres in suppressing and facilitating carcinogenesis. Curr Opin Genet Dev 10:39-46.
3. Bao S, Tibbetts RS, Brumbaugh KM, Fang Y, Richardson DA, Ali A, Chen SM, AbrahamRT, Wang XF. 2001. ATR/ATM-mediated phosphorylation of human Rad17 is required for genotoxic stress responses. Nature 411:969-974. (Pubitemid 32601496)
4. Bao S, Ouyang G, Bai X, Huang Z, Ma C, Liu M, Shao R, Anderson RM, Rich JN, Wang XF. 2004. Periostin potently promotes metastatic growth of colon cancer by augmenting cell survival via the Akt/PKB pathway. Cancer Cell 5:329-339. (Pubitemid 38482069)
5. Bao S, Wu Q, McLendon RE, Hao Y, Shi Q, Hjelmeland AB, Dewhirst MW, Bigner DD, Rich JN. 2006. Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature 444:756-760. (Pubitemid 44949604)
6. Beavon IR. 1999. Regulation of E-cadherin: Does hypoxia initiate the metastatic cascade? Mol Pathol 52:179-188.
7. Bertout JA, Patel SA, Simon MC. 2008. The impact of O2 availability on human cancer. Nat Rev Cancer 8:967-975.
8. Bindra RS, Schaffer PJ, Meng A, Woo J, Maseide K, Roth ME, Lizardi P, Hedley DW, Bristow RG, Glazer PM. 2005. Alterations in DNA repair gene expression under hypoxia: Elucidating the mechanisms of hypoxia-induced genetic instability. Ann NY Acad Sci 1059:184-195. (Pubitemid 43211621)
9. Bindra RS, Crosby ME, Glazer PM. 2007. Regulation of DNA repair in hypoxic cancer cells. Cancer Metastasis Rev 26:249-260.
10. Blagosklonny MV. 2004. Prospective strategies to enforce selectively cell death in cancer cells. Oncogene 23:2967-2975. (Pubitemid 38638856)
11. Brahimi-Horn MC, Chiche J, Pouyssegur J. 2007. Hypoxia signalling controls metabolic demand. Curr Opin Cell Biol 19:223-229. (Pubitemid 46386401)
12. Bristow RG, Hill RP. 2008. Hypoxia and metabolism. Hypoxia, DNA repair and genetic instability. Nat Rev Cancer 8:180-192.
13. Campisi J. 2005a. Senescent cells, tumor suppression, and organismal aging: Good citizens, bad neighbors. Cell 120:513-522. (Pubitemid 40269765)
14. Campisi J. 2005b. Suppressing cancer: The importance of being senescent. Science 309:886-887. (Pubitemid 41099913)
15. Campisi J, d'Adda di Fagagna F. 2007. Cellular senescence: When bad things happen to good cells. Nat Rev Mol Cell Biol 8:729-740.
16. Camps C, Buffa FM, Colella S, Moore J, Sotiriou C, Sheldon H, Harris AL, Gleadle JM, Ragoussis J. 2008. hsa-miR-210 Is induced by hypoxia and is an independent prognostic factor in breast cancer. Clin Cancer Res 14:1340-1348.
17. Cao Y, Li CY, Moeller BJ, Yu D, Zhao Y, Dreher MR, Shan S, Dewhirst MW. 2005. Observation of incipient tumor angiogenesis that is independent of hypoxia and hypoxia inducible factor-1 activation. Cancer Res 65:5498-5505. (Pubitemid 40911147)
18. Chambers AF, Groom AC, MacDonald IC. 2002. Dissemination and growth of cancer cells in metastatic sites. Nat Rev Cancer 2:563-572. (Pubitemid 37328923)
19. Chan N, Milosevic M, Bristow RG. 2007. Tumor hypoxia, DNA repair and prostate cancer progression: New targets and new therapies. Future Oncol 3:329-341. (Pubitemid 47018642)
20. Chandel NS, Simon MC. 2008. Hypoxia-inducible factor: Roles in development, physiology, and disease. Cell Death Differ 15:619-620.
21. Chang Q, Qin R, Huang T, Gao J, Feng Y. 2006. Effect of antisense hypoxia-inducible factor 1alpha on progression, metastasis, and chemosensitivity of pancreatic cancer. Pancreas 32:297-305. (Pubitemid 43753972)
22. Chen EY, Mazure NM, Cooper JA, Giaccia AJ. 2001. Hypoxia activates a platelet-derived growth factor receptor/phosphatidylinositol 3-kinase/Akt pathway that results in glycogen synthase kinase-3 inactivation. Cancer Res 61:2429-2433.
23. Coquelle A, Toledo F, Stern S, Bieth A, Debatisse M. 1998. A new role for hypoxia in tumor progression: Induction of fragile site triggering genomic rearrangements and formation of complex DMs and HSRs. Mol Cell 2:259-265. (Pubitemid 128373652)
24. Croker AK, Allan AL. 2008. Cancer stem cells: Implications for the progression and treatment of metastatic disease. J Cell Mol Med 12:374-390.
25. Dang CV, Kim JW, Gao P, Yustein J. 2008. The interplay between MYC and HIF in cancer. Nat Rev Cancer 8:51-56.
26. DeBerardinis RJ, Lum JJ, Hatzivassiliou G, Thompson CB. 2008. The biology of cancer: Metabolic reprogramming fuels cell growth and proliferation. Cell Metab 7:11-20.
27. Denko NC. 2008. Hypoxia, HIF1 and glucose metabolism in the solid tumour. Nat Rev Cancer 8:705-713.
28. 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)
29. Dong Z, Venkatachalam MA, Wang J, Patel Y, Saikumar P, Semenza GL, Force T, Nishiyama J. 2001. Up-regulation of apoptosis inhibitory protein IAP-2 by hypoxia. Hif-1-independent mechanisms. J Biol Chem 276:18702-18709. (Pubitemid 37411184)
30. Ellis LM, Hicklin DJ. 2008. VEGF-targeted therapy: Mechanisms of antitumour activity. Nat Rev Cancer 8:579-591.
31. Erler JT, Bennewith KL, Nicolau M, Dornhofer N, Kong C, Le QT, Chi JT, Jeffrey SS, Giaccia AJ. 2006. Lysyl oxidase is essential for hypoxia-induced metastasis. Nature 440:1222-1226.
32. Fang JS, Gillies RD, Gatenby RA. 2008. Adaptation to hypoxia and acidosis in carcinogenesis and tumor progression. Semin Cancer Biol 18:330-337.
33. Furuta E, Pai SK, Zhan R, Bandyopadhyay S, Watabe M, Mo YY, Hirota S, Hosobe S, Tsukada T, Miura K, Kamada S, Saito K, Iiizumi M, Liu W, Ericsson J, Watabe K. 2008. Fatty acid synthase gene is up-regulated by hypoxia via activation of Akt and sterol regulatory element binding protein-1. Cancer Res 68:1003-1011. (Pubitemid 351278386)
34. Gatenby RA, Gillies RJ. 2008. A microenvironmental model of carcinogenesis. Nat Rev Cancer 8:56-61.
35. Gatenby RA, Smallbone K, Maini PK, Rose F, Averill J, Nagle RB, Worrall L, Gillies RJ. 2007. Cellular adaptations to hypoxia and acidosis during somatic evolution of breast cancer. Br J Cancer 97:646-653. (Pubitemid 47339892)
36. Gibson SL, Bindra RS, Glazer PM. 2005. Hypoxia-induced phosphorylation of Chk2 in an ataxia telangiectasia mutated-dependent manner. Cancer Res 65:10734-10741.
37. Gibson SL, Bindra RS, Glazer PM. 2006. CHK2-dependent phosphorylation of BRCA1 in hypoxia. Radiat Res 166:646-651.
38. Gillies RJ, Gatenby RA. 2007. Hypoxia and adaptive landscapes in the evolution of carcinogenesis. Cancer Metastasis Rev 26:311-317.
39. Graeber TG, Osmanian C, Jacks T, Housman DE, Koch CJ, Lowe SW, Giaccia AJ. 1996. Hypoxia-mediated selection of cells with diminished apoptotic potential in solid tumours. Nature 379:88-91. (Pubitemid 26008141)
40. Hahn WC, Weinberg RA. 2002. Modelling the molecular circuitry of cancer. Nat Rev Cancer 2:331-341.
41. Hammond EM, Denko NC, Dorie MJ, Abraham RT, Giaccia AJ. 2002. Hypoxia links ATR and p53 through replication arrest. Mol Cell Biol 22:1834-1843.
42. Hammond EM, Dorie MJ, Giaccia AJ. 2003. ATR/ATM targets are phosphorylated by ATR in response to hypoxia and ATM in response to reoxygenation. J Biol Chem 278:12207-12213.
43. Hanahan D, Weinberg RA. 2000. The hallmarks of cancer. Cell 100:57-70.
44. Harris AL. 2002. Hypoxia-A key regulatory factor in tumour growth. Nat Rev Cancer 2:38-47. (Pubitemid 37328806)
45. Hockel M, Vaupel P. 2001. Tumor hypoxia: Definitions and current clinical, biologic, and molecular aspects. J Natl Cancer Inst 93:266-276. (Pubitemid 32219813)
46. Holash J, Maisonpierre PC, Compton D, Boland P, Alexander CR, Zagzag D, Yancopoulos GD, Wiegand SJ. 1999. Vessel cooption, regression, and growth in tumors mediated by angiopoietins and VEGF. Science 284:1994-1998. (Pubitemid 29309448)
47. Huang LE, Bindra RS, Glazer PM, Harris AL. 2007. Hypoxia-induced genetic instability-A calculated mechanism underlying tumor progression. J Mol Med 85:139-148.
48. Imai T, Horiuchi A, Wang C, Oka K, Ohira S, Nikaido T, Konishi I. 2003. Hypoxia attenuates the expression of E-cadherin via up-regulation of SNAIL in ovarian carcinoma cells. Am J Pathol 163:1437-1447. (Pubitemid 37175091)
49. Ivan M, Harris AL, Martelli F, Kulshreshtha R. 2008. Hypoxia response and microRNAs: No longer two separate worlds. J Cell Mol Med 12:1426-1431.
50. Jaakkola P, Mole DR, Tian YM, Wilson MI, Gielbert J, Gaskell SJ, Kriegsheim A, Hebestreit HF, Mukherji M, Schofield CJ, Maxwell PH, Pugh CW, Ratcliffe PJ. 2001. Targeting of HIF-alpha to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation. Science 292:468-472. (Pubitemid 32335942)
51. Jiang YG, Luo Y, He DL, Li X, Zhang LL, Peng T, Li MC, Lin YH. 2007. Role of Wnt/beta-catenin signaling pathway in epithelial-mesenchymal transition of human prostate cancer induced by hypoxia-inducible factor-1alpha. Int J Urol 14:1034-1039. (Pubitemid 47621827)
52. Joyce JA, Pollard JW. 2009. Microenvironmental regulation of metastasis. Nat Rev Cancer 9:239-252.
53. Kaelin WG, Jr., Ratcliffe PJ. 2008. Oxygen sensing by metazoans: The central role of the HIF hydroxylase pathway. Mol Cell 30:393-402.
54. Kaidi A, Williams AC, Paraskeva C. 2007. Interaction between beta-catenin and HIF-1 promotes cellular adaptation to hypoxia. Nat Cell Biol 9:210-217. (Pubitemid 46420864)
55. Kaluz S, Kaluzova M, Stanbridge EJ. 2008. Does inhibition of degradation of hypoxia-inducible factor (HIF) alpha always lead to activation of HIF? Lessons learnt from the effect of proteasomal inhibition on HIF activity. J Cell Biochem 104:536-544. (Pubitemid 351671642)
56. Kato H, Inoue T, Asanoma K, Nishimura C, Matsuda T, Wake N. 2006. Induction of human endometrial cancer cell senescence through modulation of HIF-1alpha activity by EGLN1. Int J Cancer 118:1144-1153. (Pubitemid 43185600)
57. Keith B, Simon MC. 2007. Hypoxia-inducible factors, stem cells, and cancer. Cell 129:465-472. (Pubitemid 46660978)
58. Kim WY, Sharpless NE. 2008. VHL inactivation: A new road to senescence. Cancer Cell 13:295-297.
59. Kim JW, Tchernyshyov I, Semenza GL, Dang CV. 2006. HIF-1-mediated expression of pyruvate dehydrogenase kinase: A metabolic switch required for cellular adaptation to hypoxia. Cell Metab 3:177-185. (Pubitemid 43316523)
60. Kim JW, Gao P, Dang CV. 2007. Effects of hypoxia on tumor metabolism. Cancer Metastasis Rev 26:291-298.
61. Kondo A, Safaei R, Mishima M, Niedner H, Lin X, Howell SB. 2001. Hypoxia-induced enrichment and mutagenesis of cells that have lost DNA mismatch repair. Cancer Res 61:7603-7607. (Pubitemid 32995054)
62. Koshiji M, To KK, Hammer S, Kumamoto K, Harris AL, Modrich P, Huang LE. 2005. HIF-1alpha induces genetic instability by transcriptionally down-regulating MutSalpha expression. Mol Cell 17:793-803. (Pubitemid 40386941)
63. Krishnamachary B, Berg-Dixon S, Kelly B, Agani F, Feldser D, Ferreira G, Iyer N, LaRusch J, Pak B, Taghavi P, Semenza GL. 2003. Regulation of colon carcinoma cell invasion by hypoxia-inducible factor 1. Cancer Res 63:1138-1143. (Pubitemid 36278449)
64. Krishnamachary B, Zagzag D, Nagasawa H, Rainey K, Okuyama H, Baek JH, Semenza GL. 2006. Hypoxia-inducible factor-1-dependent repression of E-cadherin in von Hippel-Lindau tumor suppressor-null renal cell carcinoma mediated by TCF3, ZFHX1A, and ZFHX1B. Cancer Res 66:2725-2731.
65. Kroemer G, Pouyssegur J. 2008. Tumor cell metabolism: Cancer's Achilles' heel. Cancer Cell 13:472-482. (Pubitemid 351766797)
66. Kulshreshtha R, Ferracin M, Wojcik SE, Garzon R, Alder H, Agosto-Perez FJ, Davuluri R, Liu CG, Croce CM, Negrini M, Calin GA, Ivan M. 2007. A microRNA signature of hypoxia. Mol Cell Biol 27:1859-1867.
67. Kunz M, Ibrahim S, Koczan D, Thiesen HJ, Kohler HJ, Acker T, Plate KH, Ludwig S, Rapp UR, Brocker EB, van Muijen GN, Flory E, Gross G. 2001. Activation of c-Jun NH2-terminal kinase/stress-activated protein kinase (JNK/SAPK) is critical for hypoxia-induced apoptosis of human malignant melanoma. Cell Growth Differ 12:137-145. (Pubitemid 32677999)
68. Laderoute KR, Alarcon RM, Brody MD, Calaoagan JM, Chen EY, Knapp AM, Yun Z, Denko NC, Giaccia AJ. 2000. Opposing effects of hypoxia on expression of the angiogenic inhibitor thrombospondin 1 and the angiogenic inducer vascular endothelial growth factor. Clin Cancer Res 6:2941-2950. (Pubitemid 30482137)
69. Lando D, Peet DJ, Gorman JJ, Whelan DA, Whitelaw ML, Bruick RK. 2002. FIH-1 is an asparaginyl hydroxylase enzyme that regulates the transcriptional activity of hypoxia-inducible factor. Genes Dev 16:1466-1471. (Pubitemid 34686328)
70. Le QT, Courter D. 2008. Clinical biomarkers for hypoxia targeting. Cancer Metastasis Rev 27:351-362.
71. Lewis C, Murdoch C. 2005. Macrophage responses to hypoxia: Implications for tumor progression and anti-cancer therapies. Am J Pathol 167:627-635. (Pubitemid 41216349)
72. Liao D, Corle C, Seagroves TN, Johnson RS. 2007. Hypoxia-inducible factor-1alpha is a key regulator of metastasis in a transgenic model of cancer initiation and progression. Cancer Res 67:563-572. (Pubitemid 46192193)
73. Lisy K, Peet DJ. 2008. Turn me on: Regulating HIF transcriptional activity. Cell Death Differ 15:642-649.
74. Lopez-Maury L, Marguerat S, Bahler J. 2008. Tuning gene expression to changing environments: From rapid responses to evolutionary adaptation. Nat Rev Genet 9:583-593.
75. Lukashev D, Ohta A, Sitkovsky M. 2007. Hypoxia-dependent antiinflammatory pathways in protection of cancerous tissues. Cancer Metastasis Rev 26:273-279.
76. Lundgren K, Holm C, Landberg G. 2007. Hypoxia and breast cancer: Prognostic and therapeutic implications. Cell Mol Life Sci 64:3233-3247.
77. Ma C, Rong Y, Radiloff DR, Datto MB, Centeno B, Bao S, Cheng AW, Lin F, Jiang S, Yeatman TJ, Wang XF. 2008. Extracellular matrix protein betaig-h3/TGFBI promotes metastasis of colon cancer by enhancing cell extravasation. Genes Dev 22:308-321. (Pubitemid 351214273)
78. Maisonpierre PC, Suri C, Jones PF, Bartunkova S, Wiegand SJ, Radziejewski C, Compton D, McClain J, Aldrich TH, Papadopoulos N, Daly TJ, Davis S, Sato TN, Yancopoulos GD. 1997. Angiopoietin-2, a natural antagonist for Tie2 that disrupts in vivo angiogenesis. Science 277:55-60. (Pubitemid 27450643)
79. Makino Y, Nakamura H, Ikeda E, Ohnuma K, Yamauchi K, Yabe Y, Poellinger L, Okada Y, Morimoto C, Tanaka H. 2003. Hypoxia-inducible factor regulates survival of antigen receptor-driven T cells. J Immunol 171:6534-6540. (Pubitemid 37532083)
80. Maxwell PH, Pugh CW, Ratcliffe PJ. 2001. Activation of the HIF pathway in cancer. Curr Opin Genet Dev 11:293-299.
81. Murata Y, Ohteki T, Koyasu S, Hamuro J. 2002. IFN-gamma and proinflammatory cytokine production by antigen-presenting cells is dictated by intracellular thiol redox status regulated by oxygen tension. Eur J Immunol 32:2866-2873. (Pubitemid 35238179)
82. Nelson DA, Tan TT, Rabson AB, Anderson D, Degenhardt K, White E. 2004. Hypoxia and defective apoptosis drive genomic instability and tumorigenesis. Genes Dev 18:2095-2107. (Pubitemid 39166627)
83. Nguyen DX, Bos PD, Massague J. 2009. Metastasis: From dissemination to organ-specific colonization. Nat Rev Cancer 9:274-284.
84. Ohh M, Park CW, Ivan M, Hoffman MA, Kim TY, Huang LE, Pavletich N, Chau V, Kaelin WG. 2000. Ubiquitination of hypoxia-inducible factor requires direct binding to the beta-domain of the von Hippel-Lindau protein. Nat Cell Biol 2:423-427. (Pubitemid 30781067)
85. Ouyang G, Liu M, Ruan K, Song G, Mao Y, Bao S. 2009. Upregulated expression of periostin by hypoxia in non-small-cell lung cancer cells promotes cell survival via the Akt/PKB pathway. Cancer Lett [Epub ahead of print].
86. Papandreou I, Cairns RA, Fontana L, Lim AL, Denko NC. 2006. HIF-1 mediates adaptation to hypoxia by actively downregulating mitochondrial oxygen consumption. Cell Metab 3:187-197.
87. Peinado H, Olmeda D, Cano A. 2007. Snail, Zeb and bHLH factors in tumour progression: An alliance against the epithelial phenotype? Nat Rev Cancer 7:415-428.
88. Polyak K, Weinberg RA. 2009. Transitions between epithelial and mesenchymal states: Acquisition of malignant and stem cell traits. Nat Rev Cancer 9:265-273.
89. Pouyssegur J, Dayan F, Mazure NM. 2006. Hypoxia signalling in cancer and approaches to enforce tumour regression. Nature 441:437-443. (Pubitemid 44050138)
90. Powis G, Kirkpatrick L. 2004. Hypoxia inducible factor-1alpha as a cancer drug target. Mol Cancer Ther 3:647-654. (Pubitemid 39193744)
91. Rangaswami H, Bulbule A, Kundu GC. 2006. Osteopontin: Role in cell signaling and cancer progression. Trends Cell Biol 16:79-87. (Pubitemid 43247403)
92. Rich JN, Bao S. 2007. Chemotherapy and cancer stem cells. Cell Stem Cell 1:353-355.
93. Richard DE, Berra E, Gothie E, Roux D, Pouyssegur J. 1999. p42/p44 mitogen-activated protein kinases phosphorylate hypoxia-inducible factor 1alpha (HIF-1alpha) and enhance the transcriptional activity of HIF-1. J Biol Chem 274:32631-32637. (Pubitemid 129535289)
94. Rius J, Guma M, Schachtrup C, Akassoglou K, Zinkernagel AS, Nizet V, Johnson RS, Haddad GG, Karin M. 2008. NF-kappaB links innate immunity to the hypoxic response through transcriptional regulation of HIF-1alpha. Nature 453:807-811. (Pubitemid 351793778)
95. Roskelley CD, Bissell MJ. 2002. The dominance of the microenvironment in breast and ovarian cancer. Semin Cancer Biol 12:97-104. (Pubitemid 34680738)
96. Ruan K, Bao S, Ouyang G. 2009. The multifaceted role of periostin in tumorigenesis. Cell Mol Life Sci [Epub ahead of print].
97. Sahlgren C, Gustafsson MV, Jin S, Poellinger L, Lendahl U. 2008. Notch signaling mediates hypoxia-induced tumor cell migration and invasion. Proc Natl Acad Sci USA 105:6392-6397. (Pubitemid 351758356)
98. Schmid T, Zhou J, Brune B. 2004. HIF-1 and p53: Communication of transcription factors under hypoxia. J Cell Mol Med 8:423-431. (Pubitemid 44145475)
99. Seimiya H, Tanji M, Oh-hara T, Tomida A, Naasani I, Tsuruo T. 1999. Hypoxia up-regulates telomerase activity via mitogen-activated protein kinase signaling in human solid tumor cells. Biochem Biophys Res Commun 260:365-370. (Pubitemid 29352071)
100. Semenza GL. 2002. HIF-1 and tumor progression: Pathophysiology and therapeutics. Trends Mol Med 8:S62-S67.
101. Semenza GL. 2003. Targeting HIF-1 for cancer therapy. Nat Rev Cancer 3:721-732.
102. Semenza GL. 2007a. Evaluation of HIF-1 inhibitors as anticancer agents. Drug Discov Today 12:853-859.
103. Semenza GL. 2007b. Life with oxygen. Science 318:62-64.
104. Shen C, Zhou Y, Zhan J, Reske SN, Buck AK. 2008. Chromosome instability and tumor lethality suppression in carcinogenesis. J Cell Biochem 105:1327-1341.
105. Shi Q, Bao S, Maxwell JA, Reese ED, Friedman HS, Bigner DD, Wang XF, Rich JN. 2004. Secreted protein acidic, rich in cysteine (SPARC), mediates cellular survival of gliomas through AKT activation. J Biol Chem 279:52200-52209. (Pubitemid 39656594)
106. Simon MC, Keith B. 2008. The role of oxygen availability in embryonic development and stem cell function. Nat Rev Mol Cell Biol 9:285-296.
107. Sitkovsky M, Lukashev D. 2005. Regulation of immune cells by local-tissue oxygen tension: HIF1 alpha and adenosine receptors. Nat Rev Immunol 5:712-721. (Pubitemid 43086172)
108. Soengas MS, Alarcon RM, Yoshida H, Giaccia AJ, Hakem R, Mak TW, Lowe SW. 1999. Apaf-1 and caspase-9 in p53-dependent apoptosis and tumor inhibition. Science 284:156-159. (Pubitemid 29282071)
109. Song G, Ouyang G, Bao S. 2005. The activation of Akt/PKB signaling pathway and cell survival. J Cell Mol Med 9:59-71.
110. Song G, Cai QF, Mao YB, Ming YL, Bao SD, Ouyang GL. 2008a. Osteopontin promotes ovarian cancer progression and cell survival and increases HIF-1alpha expression through the PI3-K/Akt pathway. Cancer Sci 99:1901-1907.
111. Song G, Ming Y, Mao Y, Bao S, Ouyang G. 2008b. Osteopontin Prevents Curcumin-Induced Apoptosis and Promotes Survival Through Akt Activation via {alpha}v{beta}3 Integrins in Human Gastric Cancer Cells. Exp Biol Med (Maywood) 233:1537-1545.
112. Sowter HM, Ratcliffe PJ, Watson P, Greenberg AH, Harris AL. 2001. HIF-1-dependent regulation of hypoxic induction of the cell death factors BNIP3 and NIX in human tumors. Cancer Res 61:6669-6673. (Pubitemid 32896483)
113. Suzuki H, Tomida A, Tsuruo T. 2001. Dephosphorylated hypoxia-inducible factor 1alpha as a mediator of p53-dependent apoptosis during hypoxia. Oncogene 20:5779-5788. (Pubitemid 32937947)
114. Talks KL, Turley H, Gatter KC, Maxwell PH, Pugh CW, Ratcliffe PJ, Harris AL. 2000. 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. (Pubitemid 30626905)
115. Wai PY, Kuo PC. 2008. Osteopontin: Regulation in tumor metastasis. Cancer Metastasis Rev 27:103-118.
116. Walsh S, Gill C, O'Neill A, Fitzpatrick JM, Watson RW. 2009. Hypoxia increases normal prostate epithelial cell resistance to receptor-mediated apoptosis via AKT activation. Int J Cancer 124:1871-1878.
117. Winner M, Leng L, Zundel W, Mitchell RA. 2007. Macrophage migration inhibitory factor manipulation and evaluation in tumoral hypoxic adaptation. Methods Enzymol 435:355-369.
118. Wouters BG, Koritzinsky M. 2008. Hypoxia signalling through mTOR and the unfolded protein response in cancer. Nat Rev Cancer 8:851-864.
119. Yang J, Mani SA, Donaher JL, Ramaswamy S, Itzykson RA, Come C, Savagner P, Gitelman I, Richardson A, Weinberg RA. 2004. Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis. Cell 117:927-939. (Pubitemid 38798858)
120. Yang MH, Wu MZ, Chiou SH, Chen PM, Chang SY, Liu CJ, Teng SC, Wu KJ. 2008. Direct regulation of TWIST by HIF-1alpha promotes metastasis. Nat Cell Biol 10:295-305.
121. Yaswen P, Campisi J. 2007. Oncogene-induced senescence pathways weave an intricate tapestry. Cell 128:233-234. (Pubitemid 46123519)
122. Young AP, Schlisio S, Minamishima YA, Zhang Q, Li L, Grisanzio C, Signoretti S, Kaelin WG, Jr. 2008. VHL loss actuates a HIF-independent senescence programme mediated by Rb and p400. Nat Cell Biol 10:361-369.
123. Zeng R, Yao Y, Han M, Zhao X, Liu XC, Wei J, Luo Y, Zhang J, Zhou J, Wang S, Ma D, Xu G. 2008. Biliverdin reductase mediates hypoxia-induced EMT via PI3-kinase and Akt. J Am Soc Nephrol 19:380-387. (Pubitemid 351240659)
124. Zhang L, Hill RP. 2004. Hypoxia enhances metastatic efficiency by up-regulating Mdm2 in KHT cells and increasing resistance to apoptosis. Cancer Res 64:4180-4189. (Pubitemid 38802421)
125. Zhang H, Gao P, Fukuda R, Kumar G, Krishnamachary B, Zeller KI, Dang CV, Semenza GL. 2007. HIF-1 inhibits mitochondrial biogenesis and cellular respiration in VHL-deficient renal cell carcinoma by repression of C-MYC activity. Cancer Cell 11:407-420. (Pubitemid 46670080)
126. Zhong H, De Marzo AM, Laughner E, Lim M, Hilton DA, Zagzag D, Buechler P, Isaacs WB, Semenza GL, Simons JW. 1999. Overexpression of hypoxia-inducible factor 1alpha in common human cancers and their metastases. Cancer Res 59:5830-5835.
127. Zundel W, Schindler C, Haas-Kogan D, Koong A, Kaper F, Chen E, Gottschalk AR, Ryan HE, Johnson RS, Jefferson AB, Stokoe D, Giaccia AJ. 2000. Loss of PTEN facilitates HIF-1-mediated gene expression. Genes Dev 14:391-396. (Pubitemid 30131884)