The role of hypoxia-inducible factors in cancer

Cellular and Molecular Life Sciences

Volumn 64, Issue 16, 2007, Pages 2170-2180

  Maynard, M A ^a   Ohh, M ^a  

^a UNIVERSITY OF TORONTO   (Canada)

Author keywords

HIF; MAPK; PHD; PI3K; VHL

Indexed keywords

ANTINEOPLASTIC AGENT; HETERODIMER; HISTONE DEACETYLASE INHIBITOR; HYPOXIA INDUCIBLE FACTOR 1; HYPOXIA INDUCIBLE FACTOR 1ALPHA; HYPOXIA INDUCIBLE FACTOR 2; MITOGEN ACTIVATED PROTEIN KINASE; PHOSPHATIDYLINOSITOL 3 KINASE; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE 3 PHOSPHATASE; PROMYELOCYTIC LEUKEMIA PROTEIN; SUCCINATE DEHYDROGENASE; TRANSCRIPTION FACTOR; TUBERIN; TUMOR SUPPRESSOR PROTEIN; UNCLASSIFIED DRUG; VON HIPPEL LINDAU PROTEIN; ISOPROTEIN; PROCOLLAGEN PROLINE 2 OXOGLUTARATE 4 DIOXYGENASE;

BREAST CANCER; CANCER GROWTH; CANCER SURVIVAL; CARCINOGENESIS; CELL TRANSFORMATION; COLORECTAL CARCINOMA; ESOPHAGUS CANCER; FIBROSARCOMA; GENE OVEREXPRESSION; HEAD AND NECK CARCINOMA; HUMAN; HYPOXIA; LUNG CANCER; LUNG NON SMALL CELL CANCER; NONHUMAN; OVARY CANCER; PROGNOSIS; PROSTATE CANCER; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; REVIEW; SOLID TUMOR; SQUAMOUS CELL CARCINOMA; STOMACH CANCER; TISSUE SPECIFICITY; TRANSACTIVATION; TRANSCRIPTION INITIATION; UPREGULATION; UTERINE CERVIX CANCER; CHEMISTRY; GENE EXPRESSION REGULATION; GENETIC TRANSCRIPTION; GENETICS; METABOLISM; NEOPLASM; PHOSPHORYLATION; PHYSIOLOGY; PROTEIN TERTIARY STRUCTURE; SIGNAL TRANSDUCTION;

GENE EXPRESSION REGULATION; HUMANS; HYPOXIA-INDUCIBLE FACTOR 1, ALPHA SUBUNIT; NEOPLASMS; PHOSPHORYLATION; PROCOLLAGEN-PROLINE DIOXYGENASE; PROTEIN ISOFORMS; PROTEIN STRUCTURE, TERTIARY; SIGNAL TRANSDUCTION; TRANSCRIPTION, GENETIC; VON HIPPEL-LINDAU TUMOR SUPPRESSOR PROTEIN;

EID: 35248814408     PISSN: 1420682X     EISSN: 15691632     Source Type: Journal    
DOI: 10.1007/s00018-007-7082-2     Document Type: Review

References (148)

1. Wang, G. L., Jiang, B. H., Rue, E. A. and Semenza, G. L. (1995) Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension. Proc. Natl. Acad. Sci. USA 92, 5510-5514.
2. Carver, L. A., Hogenesch, J. B., and Bradfield, C. A. (1994) Tissue specific expression of the rat Ah-receptor and ARNT mRNAs. Nucleic Acids Res. 22, 3038-3044.
3. Kallio, P. J., Pongratz, I., Gradin, K., McGuire, J., and Poellinger, L. (1997) Activation of hypoxia-inducible factor 1alpha: posttranscriptional regulation and conformational change by recruitment of the Arnt transcription factor. Proc. Natl. Acad. Sci. USA 94, 5667-5672.
4. Chun, Y. S., Choi, E., Kim, T. Y., Kim, M. S., and Park, J. W. (2002) A dominant-negative isoform lacking exons 11 and 12 of the human hypoxia-inducible factor-1alpha gene. Biochem. J. 362, 71-79.
5. Gothie, E., Richard, D. E., Berra, E., Pages, G., and Pouyssegur, J. (2000) Identification of alternative spliced variants of human hypoxia-inducible factor-1alpha. J. Biol. Chem. 275, 6922-6927.
6. Maynard, M. A., Qi, H., Chung, J., Lee, E. H., Kondo, Y., Hara, S., Conaway, R. C., Conaway, J. W., and Ohh, M. (2003) Multiple splice variants of the human HIF-3alpha locus are targets of the VHLE3 ubiquitin ligase complex. J. Biol. Chem. 278, 11032-11040.
7. Maynard, M. A., Evans, A. J., Hosomi, T., Hara, S., Jewett, M. A., and Ohh, M. (2005) Human HIF-3alpha4 is a dominant-negative regulator of HIF-1 and is down-regulated in renal cell carcinoma. FASEB J. 19, 1396-1406.
8. Makino, Y., Cao, R., Svensson, K., Bertilsson, G., Asman, M., Tanaka, H., Cao, Y., Berkenstam, A., and Poellinger, L. (2001) Inhibitory PAS domain protein is a negative regulator of hypoxia-inducible gene expression. Nature 414, 550-554.
9. Makino, Y., Kanopka, A., Wilson, W. J., Tanaka, H., and Poellinger, L. (2002) IPAS is an hypoxia-inducible splicing variant of the HIF-3α locus. J. Biol. Chem. 277, 32405-32408.
10. Iyer, N. V., Kotch, L. E., Agani, F., Leung, S. W., Laughner, E., Wenger, R. H., Gassmann, M., Gearhart, J. D., Lawler, A. M., Yu, A. Y. et al. (1998) Cellular and developmental control of O2 homeostasis by hypoxia-inducible factor 1 alpha. Genes Dev. 12, 149-162.
11. Ryan, H., Lo, J., and Johnson, R. (1998) HIF-1α is required for solid tumor formation and embryonic vascularization. EMBO J. 17, 3005-3015.
12. Tian, H., Hammer, R., Matsumoto, A., Russell, D., and McKnight, S. (1998) The hypoxia-responsive transcription factor EPAS1 is essential for catecholamine homeostasis and protection against heart failure during embryonic development. Genes Dev. 12, 3320-3324.
13. Hogenesch, J. B., Chan, W. K., Jackiw, V. H., Brown, R. C., Gu, Y. Z., Pray-Grant, M., Perdew, G. H., and Bradfield, C. A. (1997) Characterization of a subset of the basic-helix-loop-helix-PAS superfamily that interacts with components of the dioxin signaling pathway. J. Biol. Chem. 272, 8581-8593.
14. Wiener, C. M., Booth, G., and Semenza, G. L. (1996) In vivo expression of mRNAs encoding hypoxia-inducible factor 1. Biochem. Biophys. Res. Commun. 225, 485-488.
15. Flamme, I., Frohlich, T., von Reutern, M., Kappel, A., Damert, A., and Risau, W. (1997) HRF, a putative basic helix-loop-helix-PAS-domain transcription factor is closely related to hypoxia-inducible factor-1 alpha and developmentally expressed in blood vessels. Mech. Dev. 63, 51-60.
16. Ema, M., Taya, S., Yokotani, N., Sogawa, K., Matsuda, Y., and Fujii-Kuriyama, Y. (1997) 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.
17. Peng, J., Zhang, L., Drysdale, L., and Fong, G. H. (2000) The transcription factor EPAS-1/hypoxia-inducible factor 2alpha plays an important role in vascular remodeling. Proc. Natl. Acad. Sci. USA 97, 8386-8391.
18. Tian, H., McKnight, S. L., and Russell, D. W. (1997) Endothelial PAS domain protein 1 (EPAS1), a transcription factor selectively expressed in endothelial cells. Genes Dev. 11, 72-82.
19. Koukourakis, M. I., Giatromanolaki, A., Skarlatos, J., Corti, L., Blandamura, S., Piazza, M., Gatter, K. C., and Harris, A. L. (2001) Hypoxia inducible factor (HIF-1a and HIF-2a) expression in early esophageal cancer and response to photodynamic therapy and radiotherapy. Cancer Res. 61, 1830-1832.
20. Zhong, H., De Marzo, A., Laughner, E., Lim, M., Hilton, D., Zagzag, D., Buechler, P., Isaacs, W., Semenza, G., and Simons, J. (1999) Overexpression of hypoxia-inducible factor 1alpha in common human cancers and their metastases. Cancer Res. 59, 5830-5835.
21. Talks, K. L., Turley, H., Gatter, K. C., Maxwell, P. H., Pugh, C. W., Ratcliffe, P. J., and Harris, A. L. (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.
22. Schindl, M., Schoppmann, S. F., Samonigg, H., Hausmaninger, H., Kwasny, W., Gnant, M., Jakesz, R., Kubista, E., Birner, P., and Oberhuber, G. (2002) Overexpression of hypoxia-inducible factor 1alpha is associated with an unfavorable prognosis in lymph node-positive breast cancer. Clin. Cancer Res. 8, 1831-1837.
23. Birner, P., Schindl, M., Obermair, A., Breitenecker, G., and Oberhuber, G. (2001) Expression of hypoxia-inducible factor 1alpha in epithelial ovarian tumors: its impact on prognosis and on response to chemotherapy. Clin. Cancer Res. 7, 1661-1668.
24. Birner, P., Gatterbauer, B., Oberhuber, G., Schindl, M., Rossler, K., Prodinger, A., Budka, H., and Hainfellner, J. A. (2001) Expression of hypoxia-inducible factor-1 alpha in oligodendrogliomas: its impact on prognosis and on neoangiogenesis. Cancer 92, 165-171.
25. Birner, P., Schindl, M., Obermair, A., Plank, C., Breitenecker, G., and Oberhuber, G. (2000) Overexpression of hypoxia-inducible factor 1alpha is a marker for an unfavorable prognosis in early-stage invasive cervical cancer. Cancer Res. 60, 4693-4696.
26. Bos, R., van der Groep, P., Greijer, A. E., Shvarts, A., Meijer, S., Pinedo, H. M., Semenza, G. L., van Diest, P. J., and van der Wall, E. (2003) Levels of hypoxia-inducible factor-1alpha independently predict prognosis in patients with lymph node negative breast carcinoma. Cancer 97, 1573-1581.
27. Sivridis, E., Giatromanolaki, A., Gatter, K. C., Harris, A. L., and Koukourakis, M. I. (2002) Association of hypoxia-inducible factors 1alpha and 2alpha with activated angiogenic pathways and prognosis in patients with endometrial carcinoma. Cancer 95, 1055-1063.
28. Takahashi, R., Tanaka, S., Hiyama, T., Ito, M., Kitadai, Y., Sumii, M., Haruma, K., and Chayama, K. (2003) Hypoxia-inducible factor-1alpha expression and angiogenesis in gastrointestinal stromal tumor of the stomach. Oncol. Rep. 10, 797-802.
29. Detwiller, K. Y., Fernando, N. T., Segal, N. H., Ryeom, S. W., D'Amore, P. A., and Yoon, S. S. (2005) Analysis of hypoxia-related gene expression in sarcomas and effect of hypoxia on RNA interference of vascular endothelial cell growth factor A. Cancer Res. 65, 5881-5889.
30. Nakamura, K., Martin, K. C., Jackson, J. K., Beppu, K., Woo, C. W., and Thiele, C. J. (2006) Brain-derived neurotrophic factor activation of TrkB induces vascular endothelial growth factor expression via hypoxia-inducible factor-1alpha in neuroblastoma cells. Cancer Res. 66, 4249-4255.
31. Winter, S. C., Shah, K. A., Han, C., Campo, L., Turley, H., Leek, R., Corbridge, R. J., Cox, G. J., and Harris, A. L. (2006) The relation between hypoxia-inducible factor (HIF)-1alpha and HIF-2alpha expression with anemia and outcome in surgically treated head and neck cancer. Cancer 107, 757-766.
32. Yoshimura, H., Dhar, D. K., Kohno, H., Kubota, H., Fujii, T., Ueda, S., Kinugasa, S., Tachibana, M., and Nagasue, N. (2004) Prognostic impact of hypoxia-inducible factors 1alpha and 2alpha in colorectal cancer patients: correlation with tumor angiogenesis and cyclooxygenase-2 expression. Clin. Cancer Res. 10, 8554-8560.
33. Generali, D., Berruti, A., Brizzi, M. P., Campo, L., Bonardi, S., Wigfield, S., Bersiga, A., Allevi, G., Milani, M., Aguggini, S. et al. (2006) Hypoxia-inducible factor-1alpha expression predicts a poor response to primary chemoendocrine therapy and disease-free survival in primary human breast cancer. Clin. Cancer Res. 12, 4562-4568.
34. Liu, Y. L., Yu, J. M., Song, X. R., Wang, X. W., Xing, L. G., and Gao, B. B. (2006) 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.
35. Giatromanolaki, A., Koukourakis, M. I., Sivridis, E., Turley, H., Talks, K., Pezzella, F., Gatter, K. C., and Harris, A. L. (2001) 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.
36. Koukourakis, M. I., Giatromanolaki, A., Sivridis, E., Simopoulos, C., Turley, H., Talks, K., Gatter, K. C., and Harris, A. L. (2002) Hypoxia-inducible factor (HIF1A and HIF2A), angiogenesis, and chemoradiotherapy outcome of squamous cell head-and-neck cancer. Int. J. Radiat. Oncol. Biol. Phys. 53, 1192-1202.
37. Raval, R. R., Lau, K. W., Tran, M. G., Sowter, H. M., Mandriota, S. J., Li, J. L., Pugh, C. W., Maxwell, P. H., Harris, A. L., and Ratcliffe, P. J. (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.
38. Chen, H. H., Su, W. C., Lin, P. W., Guo, H. R., and Lee, W. Y. (2006) Hypoxia-inducible factor-1alpha correlates with MET and metastasis in node-negative breast cancer. Breast Cancer Res. Treat.[Epub ahead of print].
39. Gu, Y. Z., Moran, S. M., Hogenesch, J. B., Wartman, L., and Bradfield, C. A. (1998) Molecular characterization and chromosomal localization of a third alpha-class hypoxia inducible factor subunit, HIF3alpha. Gene Expression 7, 205-213.
40. Acker, T., Diez-Juan, A., Aragones, J., Tjwa, M., Brusselmans, K., Moons, L., Fukumura, D., Moreno-Murciano, M. P., Herbert, J. M., Burger, A., et al. (2005) Genetic evidence for a tumor suppressor role of HIF-2alpha. Cancer Cell 8, 131-141.
41. Epstein, A. C., Gleadle, J. M., McNeill, L. A., Hewitson, K. S., O'Rourke, J., Mole, D. R., Mukherji, M., Metzen, E., Wilson, M. I., Dhanda, A. et al. (2001) C. elegans EGL-9 and mammalian homologs define a family of dioxygenases that regulate HIF by prolyl hydroxylation. [see comments]. Cell 107, 43-54.
42. Bruick, R. K., and McKnight, S. L. (2001) A conserved family of prolyl-4-hydroxylases that modify HIF. Science 294, 1337-1340.
43. Huang, L. E., Gu, J., Schau, M., and Bunn, H. F. (1998) Regulation of hypoxia-inducible factor 1alpha is mediated by an O2-dependent degradation domain via the ubiquitin-proteasome pathway. Proc. Natl. Acad. Sci. USA 95, 7987-7992.
44. Srinivas, V., Zhang, L., Zhu, X., and Caro, J. (1999) Characterization of an oxygen/redox-dependent degradation domain of hypoxia-inducible factor alpha (HIF-alpha) proteins. Biochem. Biophys. Res. Commun. 260, 557-561.
45. O'Rourke, J., Tian, Y. M., Ratcliffe, P. J., and Pugh, C. W. (1999) Oxygen-regulated and transactivation domains in endothelial PAS protein 1: comparison with hypoxia-inducible factor-1a. J. Biol. Chem. 274, 2060-2071.
46. Ivan, M., Kondo, K., Yang, H., Kim, W., Valiando, J., Ohh, M., Salic, A., Asara, J. M., Lane, W. S., and Kaelin, W. G., Jr. (2001) HIFalpha targeted for VHL-mediated destruction by proline hydroxylation: implications for O2 sensing. Science 292, 464-468.
47. Jaakkola, P., Mole, D. R., Tian, Y. M., Wilson, M. I., Gielbert, J., Gaskell, S. J., Kriegsheim, A., Hebestreit, H. F., Mukherji, M., Schofield, C. J. et al. (2001) Targeting of HIF-alpha to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation. Science 292, 468-472.
48. Masson, N., Willam, C., Maxwell, P. H., Pugh, C. W., and Ratcliffe, P. J. (2001) Independent function of two destruction domains in hypoxia-inducible factor-alpha chains activated by prolyl hydroxylation. EMBO J. 20, 5197-5206.
49. Stolle, C., Glenn, G., Zbar, B., Humphrey, J., Choyke, P., Walther, M., Pack, S., Hurley, K., Andrey, C., Klausner, R. et al. (1998) Improved detection of germline mutations in the von Hippel-Lindau disease tumor suppressor gene. Hum. Mutat. 12, 417-423.
50. Clifford, S. C., Cockman, M. E., Smallwood, A. C., Mole, D. R., Woodward, E. R., Maxwell, P. H., Ratcliffe, P. J., and Maher, E. R. (2001) Contrasting effects on HIF-1alpha regulation by disease-causing pVHL mutations correlate with patterns of tumourigenesis in von Hippel-Lindau disease. Hum. Mol. Genet. 10, 1029-1038.
51. Sutter, C., Laughner, E., and Semenza, G. (2000) Hypoxia-inducible factor 1alpha protein expression is controlled by oxygen-regulated ubiquitination that is disrupted by deletions and missense mutations. Proc. Natl. Acad. Sci. USA 97, 4748-4753.
52. Shuin, T., Kondo, K., Ashida, S., Okuda, H., Yoshida, M., Kanno, H., and Yao, M. (1999) Germline and somatic mutations in von Hippel-Lindau disease gene and its significance in the development of kidney cancer. Contrib. Nephrol. 128, 1-10.
53. Shuin, T., Kondo, K., Torigoe, S., Kishida, T., Kubota, Y., Hosaka, M., Nagashima, Y., Kitamura, H., Latif, F., Zbar, B. et al. (1994) Frequent somatic mutations and loss of heterozygosity of the von Hippel-Lindau tumor suppressor gene in primary human renal cell carcinomas. Cancer Res. 54, 2852-2855.
54. Foster, K., Prowse, A., van den Berg, A., Fleming, S., Hulsbeek, M. M. F., Crossey, P. A., Richards, F. M., Cairns, P., Affara, N. A., Ferguson-Smith, M. A. et al. (1994) Somatic mutations of the von Hippel-Lindau disease tumor suppressor gene in non-familial clear cell renal carcinoma. Hum. Mol. Gen. 3, 2169-2173.
55. Kanno, H., Kondo, K., Ito, S., Yamamoto, I., Fujii, S., Torigoe, S., Sakai, N., Hosaka, M., Shuin, T., and Yao, M. (1994) Somatic mutations of the von Hippel-Lindau Tumor supressor gene in sporadic central nervous systems hemangioblastomas. Cancer Res. 54, 4845-4847.
56. Lee, J.-Y., Dong, S.-M., Park, W.-S., Yoo, N.-J., Kim, C.-S., Jang, J.-J., Chi, J.-G., Zbar, B., Lubensky, I., Linehan, W. et al. (1998) Loss of heterozygosity and somatic mutations of the VHL tumor suppressor gene in sporadic cerebellar hemangioblastomas. Cancer Res. 58, 504-508.
57. Esteban, M. A., and Maxwell, P. H. (2005) HIF, a missing link between metabolism and cancer. Nat. Med. 11, 1047-1048.
58. Laughner, E., Taghavi, P., Chiles, K., Mahon, P. C., and Semenza, G. L. (2001) HER2 (neu) signaling increases the rate of hypoxia-inducible factor 1alpha (HIF-1alpha) synthesis: novel mechanism for HIF-1-mediated vascular endothelial growth factor expression. Mol. Cell. Biol. 21, 3995-4004.
59. Zhong, H., Agani, F., Baccala, A. A., Laughner, E., Rioseco-Camacho, N., Isaacs, W. B., Simons, J. W., and Semenza, G. L. (1998) Increased expression of hypoxia inducible factor-1alpha in rat and human prostate cancer. Cancer Res. 58, 5280-5284.
60. Zundel, W., Schindler, C., Haas-Kogan, D., Koong, A., Kaper, F., Chen, E., Gottschalk, A., Ryan, H., Johnson, R., Jefferson, A. et al. (2000) Loss of PTEN facilitates HIF-1-mediated gene expression. Genes Dev. 14, 391-396.
61. Brugarolas, J. B., Vazquez, F., Reddy, A., Sellers, W. R., and Kaelin Jr, W. G. (2003) TSC2 reguates VEGF through mTOR-dependent and -independent pathways. Cancer Cell 4, 147-158.
62. Blancher, C., Moore, J. W., Robertson, N., and Harris, A. L. (2001) Effects of ras and von Hippel-Lindau (VHL) gene mutations on hypoxia-inducible factor (HIF)-1alpha, HIF-2alpha, and vascular endothelial growth factor expression and their regulation by the phosphatidylinositol 3′-kinase/Akt signaling pathway. Cancer Res. 61, 7349-7355.
63. Jiang, B. H., Jiang, G., Zheng, J. Z., Lu, Z., Hunter, T., and Vogt, P. K. (2001) Phosphatidylinositol 3-kinase signaling controls levels of hypoxia-inducible factor 1. Cell Growth Differ. 12, 363-369.
64. Fukuda, R., Hirota, K., Fan, F., Jung, Y. D., Ellis, L. M., and Semenza, G. L. (2002) Insulin-like growth factor 1 induces hypoxia-inducible factor 1-mediated vascular endothelial growth factor expression, which is dependent on MAP kinase and phosphatidylinositol 3-kinase signaling in colon cancer cells. J. Biol. Chem. 277, 38205-38211.
65. Hudson, C. C., Liu, M., Chiang, G. G., Otterness, D. M., Loomis, D. C., Kaper, F., Giaccia, A. J., and Abraham, R. T. (2002) Regulation of hypoxia-inducible factor 1alpha expression and function by the mammalian target of rapamycin. Mol. Cell. Biol. 22, 7004-7014.
66. Pore, N., Jiang, Z., Shu, H. K., Bernhard, E., Kao, G. D., and Maity, A. (2006) Akt1 activation can augment hypoxia-inducible factor-1alpha expression by increasing protein translation through a mammalian target of rapamycin-independent pathway. Mol. Cancer Res. 4, 471-479.
67. Wan, X., Shen, N., Mendoza, A., Khanna, C., and Helman, L. J. (2006) CCI-779 inhibits rhabdomyosarcoma xenograft growth by an antiangiogenic mechanism linked to the targeting of mTOR/Hif-1alpha/VEGF signaling. Neoplasia 8, 394-401.
68. Bernardi, R., Guernah, I., Jin, D., Grisendi, S., Alimonti, A., Teruya-Feldstein, J., Cordon-Cardo, C., Simon, M. C., Rafii, S., and Pandolfi, P. P. (2006) PML inhibits HIF-1alpha translation and neoangiogenesis through repression of mTOR. Nature 442, 779-785.
69. Brugarolas, J. B., Vazquez, F., Reddy, A., Sellers, W. R., and Kaelin, W. G., Jr. (2003) TSC2 regulates VEGF through mTOR-dependent and -independent pathways. Cancer Cell 4, 147-158.
70. Kietzmann, T., and Gorlach, A. (2005) Reactive oxygen species in the control of hypoxia-inducible factor-mediated gene expression. Semin. Cell Dev. Biol. 16, 474-486.
71. Quintero, M., Brennan, P. A., Thomas, G. J., and Moncada, S. (2006) Nitric oxide is a factor in the stabilization of hypoxia-inducible factor-1alpha in cancer: role of free radical formation. Cancer Res. 66, 770-774.
72. Maranchie, J. K., and Zhan, Y. (2005) Nox4 is critical for hypoxia-inducible factor 2-alpha transcriptional activity in von Hippel-Lindau-deficient renal cell carcinoma. Cancer Res. 65, 9190-9193.
73. Jiang, B. H., Rue, E., Wang, G. L., Roe, R., and Semenza, G. L. (1996) Dimerization, DNA binding, and transactivation properties of hypoxia-inducible factor 1. J. Biol. Chem. 271, 17771-17778.
74. Jiang, B. H., Zheng, J. Z., Leung, S. W., Roe, R., and Semenza, G. L. (1997) Transactivation and inhibitory domains of hypoxia-inducible factor 1a. J. Biol. Chem. 272, 19253-19260.
75. Pugh, C., O'Rourke, J., Nagao, M., Gleadle, J., and Ratcliffe, P. (1997) Activation of hypoxia-inducible factor-1; definition of regulatory domains within the alpha subunit. J. Biol. Chem. 272, 11205-11214.
76. Hara, S., Hamada, J., Kobayashi, C., Kondo, Y., and Imura, N. (2001) Expression and characterization of hypoxia-inducible factor (HIF)-3alpha in human kidney: suppression of HIF-mediated gene expression by HIF-3alpha. Biochem. Biophys. Res. Commun. 287, 808-813.
77. Ema, M., Hirota, K., Mimura, J., Abe, H., Yodoi, J., Sogawa, K., Poellinger, L. and Fukii-Kuriyama, Y. (1999) Molecular mechanisms of transcription activation by HLFand HIF1a in response to hypoxia: their stabilization and redox signal-induced interaction with CBP/p300. EMBO J. 18, 1905-1914.
78. Kallio, P. J., Okamoto, K., O'Brien, S., Carrero, P., Makino, Y., Tanaka, H., and Poellinger, L. (1998) Signal transduction in hypoxic cells: inducible nuclear translocation and recruitment of the CBP/p300 coactivator by the hypoxia-inducible factor-1alpha. EMBO J. 17, 6573-6586.
79. Carrero, P., Okamoto, K., Coumailleau, P., O'Brien, S., Tanaka, H., and Poellinger, L. (2000) Redox-regulated recruitment of the transcriptional coactivators CREB-binding protein and SRC-1 to hypoxia-inducible factor 1alpha. Mol. Cell. Biol. 20, 402-415.
80. Arany, Z., Huang, L. E., Eckner, R., Bhattacharya, S., Jiang, C., Goldberg, M. A., Bunn, H. F., and Livingston, D. M. (1996) An essential role for p300/CBP in the cellular response to hypoxia. Proc. Nat. Acad. Sci. of the USA 93, 12969-12973.
81. Yan, Q., Bartz, S., Mao, M., Li, L., and Kaelin, W. G., Jr. (2007) The HIF2{alpha} N-terminal and C-terminal transactivation domains cooperate to promote renal tumorigenesis in vivo. Mol. Cell. Biol. 27, 2092-2102.
82. Pereira, T., Zheng, X., Ruas, J. L., Tanimoto, K., and Poellinger, L. (2003) Identification of residues critical for regulation of protein stability and the transactivation function of the hypoxia-inducible factor-1alpha by the von Hippel-Lindau tumor suppressor gene product. J. Biol. Chem. 278, 6816-6823.
83. Freedman, S. J., Sun, Z. Y., Poy, F., Kung, A. L., Livingston, D. M., Wagner, G., and Eck, M. J. (2002) Structural basis for recruitment of CBP/p300 by hypoxia-inducible factor-1 alpha. Proc. Natl. Acad. Sci. USA 99, 5367-5372.
84. Lando, D., Peet, D. J., Whelan, D. A., Gorman, J. J., and Whitelaw, M. L. (2002) Asparagine hydroxylation of the HIF transactivation domain a hypoxic switch. Science 295, 858-861.
85. Kasper, L. H., Boussouar, F., Boyd, K., Xu, W., Biesen, M., Rehg, J., Baudino, T. A., Cleveland, J. L., and Brindle, P. K. (2005) Two transactivation mechanisms cooperate for the bulk of HIF-1-responsive gene expression. EMBO J. 24, 3846-3858.
86. Kato, H., Tamamizu-Kato, S., and Shibasaki, F. (2004) Histone deacetylase 7 associates with hypoxia-inducible factor 1alpha and increases transcriptional activity. J. Biol. Chem. 279, 41966-41974.
87. Qian, D. Z., Kachhap, S. K., Collis, S. J., Verheul, H. M., Carducci, M. A., Atadja, P., and Pili, R. (2006) Class II histone deacetylases are associated with VHL-independent regulation of hypoxia-inducible factor 1{alpha}. Cancer Res. 66, 8814-8821.
88. Bilton, R., Mazure, N., Trottier, E., Hattab, M., Dery, M. A., Richard, D. E., Pouyssegur, J., and Brahimi-Horn, M. C. (2005) Arrest-defective-1 protein, an acetyltransferase, does not alter stability of hypoxia-inducible factor (HIF)-1alpha and is not induced by hypoxia or HIF. J. Biol. Chem. 280, 31132-31140.
89. Fisher, T. S., Etages, S. D., Hayes, L., Crimin, K., and Li, B. (2005) Analysis of ARD1 function in hypoxia response using retroviral RNA interference. J. Biol. Chem. 280, 17749-17757.
90. Arnesen, T., Kong, X., Evjenth, R., Gromyko, D., Varhaug, J. E., Lin, Z., Sang, N., Caro, J., and Lillehaug, J. R. (2005) Interaction between HIF-1 alpha (ODD) and hARD1 does not induce acetylation and destabilization of HIF-1 alpha. FEBS Lett. 579, 6428-6432.
91. Kim, S. H., Park, J. A., Kim, J. H., Lee, J. W., Seo, J. H., Jung, B. K., Chun, K. H., Jeong, J. W., Bae, M. K., and Kim, K. W. (2006) Characterization of ARD1 variants in mammalian cells. Biochem. Biophys. Res. Commun. 340, 422-427.
92. Jeong, J. W., Bae, M. K., Ahn, M. Y., Kim, S. H., Sohn, T. K., Bae, M. H., Yoo, M. A., Song, E. J., Lee, K. J., and Kim, K. W. (2002) Regulation and destabilization of HIF-1alpha by ARD1-mediated acetylation. Cell 111, 709-720.
93. Sang, N., Stiehl, D. P., Bohensky, J., Leshchinsky, I., Srinivas, V., and Caro, J. (2003) MAPK signaling up-regulates the activity of hypoxia-inducible factors by its effects on p300. J. Biol. Chem. 278, 14013-14019.
94. Minet, E., Arnould, T., Michel, G., Roland, I., Mottet, D., Raes, M., Remacle, J., and Michiels, C. (2000) ERK activation upon hypoxia: involvement in HIF-1 activation. FEBS Lett. 468, 53-58.
95. Das, B., Yeger, H., Tsuchida, R., Torkin, R., Gee, M. F., Thorner, P. S., Shibuya, M., Malkin, D., and Baruchel, S. (2005) A hypoxia-driven vascular endothelial growth factor/Flt1 autocrine loop interacts with hypoxia-inducible factor-1alpha through mitogen-activated protein kinase/extracellular signal-regulated kinase 1/2 pathway in neuroblastoma. Cancer Res. 65, 7267-7275.
96. Mylonis, I., Chachami, G., Samiotaki, M., Panayotou, G., Paraskeva, E., Kalousi, A., Georgatsou, E., Bonanou, S., and Simos, G. (2006) Identification of MAPK phosphorylation sites and their role in the localization and activity of hypoxia-inducible factor-1alpha. J. Biol. Chem. 281, 33095-33106.
97. Dayan, F., Roux, D., Brahimi-Horn, M. C., Pouyssegur, J., and Mazure, N. M. (2006) The oxygen sensor factor-inhibiting hypoxia-inducible factor-1 controls expression of distinct genes through the bifunctional transcriptional character of hypoxia-inducible factor-1alpha. Cancer Res. 66, 3688-3698.
98. Ryan, H. E., Lo, J., and Johnson, R. S. (1998) HIF-1 alpha is required for solid tumor formation and embryonic vascularization. EMBO J. 17, 3005-3015.
99. Carmeliet, P., Dor, Y., Herbert, J. M., Fukumura, D., Brusselmans, K., Dewerchin, M., Neeman, M., Bono, F., Abramovitch, R., Maxwell, P. et al. (1998) Role of HIF-1alpha in hypoxia-mediated apoptosis, cell proliferation and tumour angiogenesis. Nature 394, 485-490.
100. Wiesener, M. S., Turley, H., Allen, W. E., Willam, C., Eckardt, K. U., Talks, K. L., Wood, S. M., Gatter, K. C., Harris, A. L., Pugh, C. W. et al. (1998) Induction of endothelial PAS domain protein-1 by hypoxia: characterization and comparison with hypoxia-inducible factor-1alpha. Blood 92, 2260-2268.
101. Folkman, J. (1992) The role of angiogenesis in tumor growth. Semin. Cancer Biol. 3, 65-71.
102. Chang, Y. S., di Tomaso, E., McDonald, D. M., Jones, R., Jain, R. K., and Munn, L. L. (2000) Mosaic blood vessels in tumors: frequency of cancer cells in contact with flowing blood. Proc. Natl. Acad. Sci. USA 97, 14608-14613.
103. Vaupel, P., Thews, O., and Hoeckel, M. (2001) Treatment resistance of solid tumors: role of hypoxia and anemia. Med. Oncol. 18, 243-259.
104. Vaupel, P., Kelleher, D. K., and Hockel, M. (2001) Oxygen status of malignant tumors: pathogenesis of hypoxia and significance for tumor therapy. Semin. Oncol. 28, 29-35.
105. Caniggia, I., Mostachfi, H., Winter, J., Gassmann, M., Lye, S. J., Kuliszewski, M., and Post, M. (2000) Hypoxia-inducible factor-1 mediates the biological effects of oxygen on human trophoblast differentiation through TGFbeta(3). J. Clin. Invest. 105, 577-587.
106. Grosfeld, A., Andre, J., Hauguel-De Mouzon, S., Berra, E., Pouyssegur, J., and Guerre-Millo, M. (2002) Hypoxia-inducible factor 1 transactivates the human leptin gene promoter. J. Biol. Chem. 277, 42953-42957.
107. Sanchez-Elsner, T., Botella, L. M., Velasco, B., Langa, C., and Bernabeu, C. (2002) Endoglin expression is regulated by transcriptional cooperation between the hypoxia and transforming growth factor-beta pathways. J. Biol. Chem. 277, 43799-43808.
108. Bodi, I., Bishopric, N. H., Discher, D. J., Wu, X., and Webster, K. A. (1995) Cell-specificity and signaling pathway of endothelin-1 gene regulation by hypoxia. Cardiovasc. Res. 30, 975-984.
109. Eckhart, A. D., Yang, N., Xin, X., and Faber, J. E. (1997) Characterization of the alpha1B-adrenergic receptor gene promoter region and hypoxia regulatory elements in vascular smooth muscle. Proc. Natl. Acad. Sci. USA 94, 9487-9492.
110. Hu, J., Discher, D. J., Bishopric, N. H., and Webster, K. A. (1998) Hypoxia regulates expression of the endothelin-1 gene through a proximal hypoxia-inducible factor-1 binding site on the antisense strand. Biochem. Biophys. Res. Commun 245, 894-899.
111. Lee, P. J., Jiang, B. H., Chin, B. Y., Iyer, N. V., Alam, J., Semenza, G. L., and Choi, A. M. (1997) Hypoxia-inducible factor-1 mediates transcriptional activation of the heme oxygenase-1 gene in response to hypoxia. J. Biol. Chem. 272, 5375-5381.
112. Melillo, G., Musso, T., Sica, A., Taylor, L., Cox, G., and Varesio, L. (1995) A hypoxia-responsive element mediates a novel pathway of activation of the inducible nitric oxide synthase promoter. J. Exp. Med. 182, 1683-1693.
113. Palmer, L., Semenza, G., Stoler, M., and Johns, R. (1998) Hypoxia induces type II NOS gene expression in pulmonary artery endothelial cells via HIF-1. Am. J. Physiol. 274, L212-219.
114. Elvert, G., Kappel, A., Heidenreich, R., Englmeier, U., Lanz, S., Acker, T., Rauter, M., Plate, K., Sieweke, M., Breier, G. etal. (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.
115. Chen, J., Zhao, S., Nakada, K., Kuge, Y., Tamaki, N., Okada, F., Wang, J., Shindo, M., Higashino, F., Takeda, K. et al. (2003) Dominant-negative hypoxia-inducible factor-1 alpha reduces tumorigenicity of pancreatic cancer cells through the suppression of glucose metabolism. Am. J. Pathol. 162, 1283-1291.
116. Akakura, N., Kobayashi, M., Horiuchi, I., Suzuki, A., Wang, J., Chen, J., Niizeki, H., Kawamura, K., Hosokawa, M., and Asaka, M. (2001) Constitutive expression of hypoxia-inducible factor-1alpha renders pancreatic cancer cells resistant to apoptosis induced by hypoxia and nutrient deprivation. Cancer Res. 61, 6548-6554.
117. Lu, H., Forbes, R. A., and Verma, A. (2002) Hypoxia-inducible factor 1 activation by aerobic glycolysis implicates the Warburg effect in carcinogenesis. J. Biol. Chem. 277, 23111-23115.
118. Lu, H., Dalgard, C. L., Mohyeldin, A., McFate, T., Tait, A. S., and Verma, A. (2005) Reversible inactivation of HIF-1 prolyl hydroxylases allows cell metabolism to control basal HIF-1. J. Biol. Chem. 280, 41928-41939.
119. Gunaratnam, L., Morley, M., Franovic, A., de Paulsen, N., Mekhail, K., Parolin, D. A., Nakamura, E., Lorimer, I. A., and Lee, S. (2003) Hypoxia inducible factor activates the transforming growth factor-alpha/epidermal growth factor receptor growth stimulatory pathway in VHL(-/-) renal cell carcinoma cells. J. Biol. Chem. 278, 44966-44974.
120. Yoon, D. Y., Buchler, P., Saarikoski, S. T., Hines, O. J., Reber, H. A., and Hankinson, O. (2001) Identification of genes differentially induced by hypoxia in pancreatic cancer cells. Biochem. Biophys. Res. Commun. 288, 882-886.
121. Graham, C. H., Forsdike, J., Fitzgerald, C. J., and Macdonald-Goodfellow, S. (1999) Hypoxia-mediated stimulation of carcinoma cell invasiveness via upregulation of urokinase receptor expression. Int. J. Cancer 80, 617-623.
122. Krishnamachary, B., Berg-Dixon, S., Kelly, B., Agani, F., Feldser, D., Ferreira, G., Iyer, N., LaRusch, J., Pak, B., Taghavi, P. et al. (2003) Regulation of colon carcinoma cell invasion by hypoxia-inducible factor 1. Cancer Res. 63, 1138-1143.
123. Erler, J. T., Bennewith, K. L., Nicolau, M., Dornhofer, N., Kong, C., Le, Q. T., Chi, J. T., Jeffrey, S. S., and Giaccia, A. J. (2006) Lysyl oxidase is essential for hypoxia-induced metastasis. Nature 440, 1222-1226.
124. Evans, A. J., Russell, R. C., Roche, O., Burry, T. N., Fish, J. E., Chow, V. W., Kim, W. Y., Saravanan, A., Maynard, M. A., Gervais, M. L. et al. (2007) VHL promotes E2 box-dependent E-cadherin transcription by HIF-mediated regulation of SIP1 and snail. Mol. Cell. Biol. 27, 157-169.
125. Esteban, M. A., Tran, M. G., Harten, S. K., Hill, P., Castellanos, M. C., Chandra, A., Raval, R., O'Brien T, S., and Maxwell, P. H. (2006) Regulation of E-cadherin expression by VHL and hypoxia-inducible factor. Cancer Res. 66, 3567-3575.
126. Krishnamachary, B., Zagzag, D., Nagasawa, H., Rainey, K., Okuyama, H., Baek, J. H., and Semenza, G. L. (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.
127. Schioppa, T., Uranchimeg, B., Saccani, A., Biswas, S. K., Doni, A., Rapisarda, A., Bernasconi, S., Saccani, S., Nebuloni, M., Vago, L. et al. (2003) Regulation of the chemokine receptor CXCR4 by hypoxia. J. Exp. Med. 198, 1391-1402.
128. Melillo, G. (2006) Inhibiting hypoxia-inducible factor 1 for cancer therapy. Mol. Cancer Res. 4, 601-605.
129. Nelson, W. J., and Nusse, R. (2004) Convergence of Wnt, beta-catenin, and cadherin pathways. Science 303, 1483-1487.
130. Feldser, D., Agani, F., Iyer, N. V., Pak, B., Ferreira, G., and Semenza, G. L. (1999) Reciprocal positive regulation of hypoxia-inducible factor 1alpha and insulin-like growth factor 2. Cancer Res. 59, 3915-3918.
131. Tazuke, S. I., Mazure, N. M., Sugawara, J., Carland, G., Faessen, G. H., Suen, L. F., Irwin, J. C., Powell, D. R., Giaccia, A. J., and Giudice, L. C. (1998) Hypoxia stimulates insulin-like growth factor binding protein 1 (IGFBP-1) gene expression in HepG2 cells: a possible model for IGFBP-1 expression in fetal hypoxia. Proc. Natl. Acad. Sci. USA 95, 10188-10193.
132. Zhang, S. X., Gozal, D., Sachleben, L. R., Jr., Rane, M., Klein, J. B., and Gozal, E. (2003) Hypoxia induces an autocrine-paracrine survival pathway via platelet-derived growth factor (PDGF)-B/PDGF-beta receptor/phosphatidylinositol 3-kinase/Akt signaling in RN46A neuronal cells. FASEB J. 17, 1709-1711.
133. Pause, A., Lee, S., Lonergan, K. M., and Klausner, R. D. (1998) The von Hippel-Lindau tumor suppressor gene is required for cell cycle exit upon serum withdrawal. Proc. Natl. Acad. Sci. (USA) 95, 993-998.
134. Kaidi, A., Qualtrough, D., Williams, A. C., and Paraskeva, C. (2006) Direct transcriptional up-regulation of cyclooxygenase-2 by hypoxia-inducible factor (HIF)-1 promotes colorectal tumor cell survival and enhances HIF-1 transcriptional activity during hypoxia. Cancer Res. 66, 6683-6691.
135. Peng, X. H., Karna, P., Cao, Z., Jiang, B. H., Zhou, M., and Yang, L. (2006) Cross-talk between epidermal growth factor receptor and hypoxia-inducible factor-1alpha signal pathways increases resistance to apoptosis by up-regulating survivin gene expression. J. Biol. Chem. 281, 25903-25914.
136. Bruick, R. K. (2000) Expression of the gene encoding the proapoptotic Nip3 protein is induced by hypoxia. Proc. Natl. Acad. Sci. USA 97, 9082-9087.
137. Sowter, H. M., Ratcliffe, P. J., Watson, P., Greenberg, A. H., and Harris, A. L. (2001) HIF-1-dependent regulation of hypoxic induction of the cell death factors BNIP3 and NIX in human tumors. Cancer Res. 61, 6669-6673.
138. Shoshani, T., Faerman, A., Mett, I., Zelin, E., Tenne, T., Gorodin, S., Moshel, Y., Elbaz, S., Budanov, A., Chajut, A. et al. (2002) Identification of a novel hypoxia-inducible factor 1-responsive gene, RTP801, involved in apoptosis. Mol. Cell. Biol. 22, 2283-2293.
139. Bacon, A. L., Fox, S., Turley, H., and Harris, A. L. (2007) Selective silencing of the hypoxia-inducible factor 1 target gene BNIP3 by histone deacetylation and methylation in colorectal cancer. Oncogene 26, 132-141.
140. Wartenberg, M., Ling, F. C., Muschen, M., Klein, F., Acker, H., Gassmann, M., Petrat, K., Putz, V., Hescheler, J., and Sauer, H. (2003) Regulation of the multidrug resistance transporter P-glycoprotein in multicellular tumor spheroids by hypoxia-inducible factor (HIF-1) and reactive oxygen species. FASEB J. 17, 503-505.
141. Unruh, A., Ressel, A., Mohamed, H. G., Johnson, R. S., Nadrowitz, R., Richter, E., Katschinski, D. M., and Wenger, R. H. (2003) The hypoxia-inducible factor-1 alpha is a negative factor for tumor therapy. Oncogene 22, 3213-3220.
142. Nishi, H., Nakada, T., Kyo, S., Inoue, M., Shay, J. W., and Isaka, K. (2004) Hypoxia-inducible factor 1 mediates upregulation of telomerase (hTERT). Mol. Cell. Biol. 24, 6076-6083.
143. Yatabe, N., Kyo, S., Maida, Y., Nishi, H., Nakamura, M., Kanaya, T., Tanaka, M., Isaka, K., Ogawa, S., and Inoue, M. (2004) HIF-1-mediated activation of telomerase in cervical cancer cells. Oncogene 23, 3708-3715.
144. Stewart, S. A., and Weinberg, R. A. (2006) Telomeres: cancer to human aging. Annu. Rev. Cell Dev. Biol. 22, 531-557.
145. Carroll, V. A., and Ashcroft, M. (2006) Role of hypoxia-inducible factor (HIF)-1alpha versus HIF-2alpha in the regulation of HIF target genes in response to hypoxia, insulin-like growth factor-I, or loss of von Hippel-Lindau function: implications for targeting the HIF pathway. Cancer Res. 66, 6264-6270.
146. Aprelikova, O., Wood, M., Tackett, S., Chandramouli, G. V., and Barrett, J. C. (2006) Role of ETS transcription factors in the hypoxia-inducible factor-2 target gene selection. Cancer Res. 66, 5641-5647.
147. Covello, K. L., Kehler, J., Yu, H., Gordan, J. D., Arsham, A. M., Hu, C. J., Labosky, P. A., Simon, M. C., and Keith, B. (2006) HIF-2alpha regulates Oct-4: effects of hypoxia on stem cell function, embryonic development, and tumor growth. Genes Dev. 20, 557-570.
148. Warnecke, C., Zaborowska, Z., Kurreck, J., Erdmann, V. A., Frei, U., Wiesener, M., and Eckardt, K. U. (2004) Differentiating the functional role of hypoxia-inducible factor (HIF)-1alpha and HIF-2alpha (EPAS-1) by the use of RNA interference: erythropoietin is a HIF-2alpha target gene in Hep3B and Kelly cells. FASEB J. 18, 1462-1464.