Regulation of cancer cell metabolism by hypoxia-inducible factor 1

Targeting HIF-1 for cancer therapy

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Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension.

Wang, G. L., Jiang, B. H., Rue, E. A., & Semenza, G. L. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.12.5510 · Cited by 6,212

Targeting of HIF-α to the von Hippel-Lindau Ubiquitylation Complex by O 2 -Regulated Prolyl Hydroxylation

Jaakkola, P., Mole, D. R., Tian, Y.-M., Wilson, M. I., Gielbert, J., Gaskell, S. J., Kriegsheim, A. V., Hebestreit, H. F., Mukherji, M., Schofield, C. J., et al. (2001) · Science · doi:10.1126/science.1059796 · Cited by 5,535

The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis

Maxwell, P. H., Wiesener, M. S., Chang, G.-W., Clifford, S. C., Vaux, E. C., Cockman, M. E., Wykoff, C. C., Pugh, C. W., Maher, E. R., & Ratcliffe, P. J. (1999) · Nature · doi:10.1038/20459 · Cited by 5,180

HIFα Targeted for VHL-Mediated Destruction by Proline Hydroxylation: Implications for O 2 Sensing

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HIF-1-mediated expression of pyruvate dehydrogenase kinase: A metabolic switch required for cellular adaptation to hypoxia

Kim, J.-W., Tchernyshyov, I., Semenza, G. L., & Dang, C. V. (2006) · Cell Metabolism · doi:10.1016/j.cmet.2006.02.002 · Cited by 3,905

C. elegans EGL-9 and mammalian homologs define a family of dioxygenases that regulate HIF by prolyl hydroxylation

Epstein, A. C. R., 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) · Cell · doi:10.1016/s0092-8674(01)00507-4 · Cited by 3,333

Discovery and development of bevacizumab, an anti-VEGF antibody for treating cancer

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Cellular and developmental control of O 2 homeostasis by hypoxia-inducible factor 1α

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Tumor cell metabolism: cancer's Achilles' heel

Kroemer, G., & Pouyssegur, J. (2008) · Cancer Cell · doi:10.1016/j.ccr.2008.05.005 · Cited by 2,337

HIF-1 mediates adaptation to hypoxia by actively downregulating mitochondrial oxygen consumption

Papandreou, I., Cairns, R. A., Fontana, L., Lim, A. L., & Denko, N. C. (2006) · Cell Metabolism · doi:10.1016/j.cmet.2006.01.012 · Cited by 2,267

Hypoxia in cancer: significance and impact on clinical outcome

Vaupel, P., & Mayer, A. (2007) · Cancer and Metastasis Reviews · doi:10.1007/s10555-007-9055-1 · Cited by 2,240

Regulation of hypoxia-inducible factor 1α is mediated by an O 2 -dependent degradation domain via the ubiquitin-proteasome pathway

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Purification and Characterization of Hypoxia-inducible Factor 1

Wang, G. L., & Semenza, G. L. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.3.1230 · Cited by 2,094

Hypoxia signalling in cancer and approaches to enforce tumour regression

Pouysségur, J., Dayan, F., & Mazure, N. M. (2006) · Nature · doi:10.1038/nature04871 · Cited by 1,676

Hypoxia-inducible Factor 1α (HIF-1α) Protein Is Rapidly Degraded by the Ubiquitin-Proteasome System under Normoxic Conditions

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Attenuation of LDH-A expression uncovers a link between glycolysis, mitochondrial physiology, and tumor maintenance

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FIH-1 is an asparaginyl hydroxylase enzyme that regulates the transcriptional activity of hypoxia-inducible factor

Lando, D., Peet, D. J., Gorman, J. J., Whelan, D. A., Whitelaw, M. L., & Bruick, R. K. (2002) · Genes & Development · doi:10.1101/gad.991402 · Cited by 1,550

Mitochondrial complex III is required for hypoxia-induced ROS production and cellular oxygen sensing

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HIF-1 Regulates Cytochrome Oxidase Subunits to Optimize Efficiency of Respiration in Hypoxic Cells

Fukuda, R., Zhang, H., Kim, J.-W., Shimoda, L., Dang, C. V., & Semenza, G. L. (2007) · Cell · doi:10.1016/j.cell.2007.01.047 · Cited by 1,225

Hypoxia-inducible factor 1 levels vary exponentially over a physiologically relevant range of O2 tension

Jiang, B. H., Semenza, G. L., Bauer, C., & Marti, H. H. (1996) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1996.271.4.c1172 · Cited by 1,213

Transcriptional regulation of vascular endothelial cell responses to hypoxia by HIF-1

Manalo, D. J., Rowan, A., Lavoie, T., Natarajan, L., Kelly, B. D., Ye, S. Q., Garcia, J. G. N., & Semenza, G. L. (2005) · Blood · doi:10.1182/blood-2004-07-2958 · Cited by 1,154

c-Myc transactivation of LDH-A : Implications for tumor metabolism and growth

Shim, H., Dolde, C., Lewis, B. C., Wu, C.-S., Dang, G., Jungmann, R. A., Dalla-Favera, R., & Dang, C. V. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.13.6658 · Cited by 1,092

Cycling hypoxia and free radicals regulate angiogenesis and radiotherapy response

Dewhirst, M. W., Cao, Y., & Moeller, B. (2008) · Nature Reviews Cancer · doi:10.1038/nrc2397 · Cited by 1,022

HIF-1 inhibits mitochondrial biogenesis and cellular respiration in VHL-deficient renal cell carcinoma by repression of C-MYC activity

Zhang, H., Gao, P., Fukuda, R., Kumar, G., Krishnamachary, B., Zeller, K. I., Dang, C. V., & Semenza, G. L. (2007) · Cancer Cell · doi:10.1016/j.ccr.2007.04.001 · Cited by 885

THE METABOLISM OF TUMORS

WARBURN, O., & Dickens, F. (1931) · The American Journal of the Medical Sciences · doi:10.1097/00000441-193107000-00022 · Cited by 815

HIF-1α binding to VHL is regulated by stimulus-sensitive proline hydroxylation

Yu, F., White, S. B., Zhao, Q., & Lee, F. S. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.181341498 · Cited by 796

Regulation of the Hypoxia-inducible Transcription Factor 1α by the Ubiquitin-Proteasome Pathway

Kallio, P. J., Wilson, W. J., O’Brien, S. L., Makino, Y., & Poellinger, L. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.10.6519 · Cited by 754

Hypoxia: A key regulator of angiogenesis in cancer

Liao, D., & Johnson, R. S. (2007) · Cancer and Metastasis Reviews · doi:10.1007/s10555-007-9066-y · Cited by 737

Activation of HIF1α ubiquitination by a reconstituted von Hippel-Lindau (VHL) tumor suppressor complex

Kamura, T., Sato, S., Iwaï, K., Czyzyk-Krzeska, M., Conaway, R. C., & Conaway, J. W. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.190332597 · Cited by 652

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Mitochondrial dysfunction resulting from loss of cytochrome c impairs cellular oxygen sensing and hypoxic HIF-α activation

Mansfield, K. D., Guzy, R. D., Pan, Y., Young, R. M., Cash, T. P., Schumacker, P. T., & Simon, M. C. (2005) · Cell Metabolism · doi:10.1016/j.cmet.2005.05.003 · Cited by 606

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Elevated tumor lactate concentrations predict for an increased risk of metastases in head-and-neck cancer

Brizel, D. M., Schroeder, T., Scher, R. L., Walenta, S., Clough, R. W., Dewhirst, M. W., & Mueller‐Klieser, W. (2001) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/s0360-3016(01)01630-3 · Cited by 596

HIF-Dependent Antitumorigenic Effect of Antioxidants In Vivo

Gao, P., Zhang, H., Dinavahi, R., Li, F., Xiang, Y., Raman, V., Bhujwalla, Z. M., Felsher, D. W., Cheng, L., Pevsner, J., et al. (2007) · Cancer Cell · doi:10.1016/j.ccr.2007.08.004 · Cited by 523

Levels of hypoxia‐inducible factor‐1α independently predict prognosis in patients with lymph node negative breast carcinoma

Bos, R., van der Groep, P., Greijer, A. E., Shvarts, A., Meijer, S., Pinedo, H. M., Semenza, G. L., van Diest, P. J., & van der Wall, E. (2003) · Cancer · doi:10.1002/cncr.11246 · Cited by 500

RACK1 Competes with HSP90 for Binding to HIF-1α and Is Required for O2-Independent and HSP90 Inhibitor-Induced Degradation of HIF-1α

Liu, Y. V., Baek, J. H., Zhang, H., Diez, R., Cole, R. N., & Semenza, G. L. (2007) · Molecular Cell · doi:10.1016/j.molcel.2007.01.001 · Cited by 490

Targeting tumor-associated carbonic anhydrase IX in cancer therapy

Thiry, A., Dogné, J., Masereel, B., & Supuran, C. T. (2006) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2006.09.002 · Cited by 396

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Heterozygous HIF‐1α deficiency impairs carotid body‐mediated systemic responses and reactive oxygen species generation in mice exposed to intermittent hypoxia

Peng, Y., Yuan, G., Ramakrishnan, D., Sharma, S. D., Bosch‐Marcé, M., Kumar, G. K., Semenza, G. L., & Prabhakar, N. R. (2006) · The Journal of Physiology · doi:10.1113/jphysiol.2006.114033 · Cited by 365

Evaluation of HIF-1 inhibitors as anticancer agents

Semenza, G. L. (2007) · Drug Discovery Today · doi:10.1016/j.drudis.2007.08.006 · Cited by 363

β-catenin mutation and overexpression in hepatocellular carcinoma

Wong, C., Fan, S. T., & Ng, I. O. (2001) · Cancer · doi:10.1002/1097-0142(20010701)92:1 · Cited by 353

Vasculogenesis, angiogenesis, and arteriogenesis: Mechanisms of blood vessel formation and remodeling

Semenza, G. L. (2007) · Journal of Cellular Biochemistry · doi:10.1002/jcb.21523 · Cited by 329

Expression of hypoxia-inducible factor 1alpha in epithelial ovarian tumors: its impact on prognosis and on response to chemotherapy.

Birner, P., Schindl, M., Obermair, A., Breitenecker, G., & Oberhuber, G. (2001) · PubMed · Cited by 310

Adaptation to hypoxia and acidosis in carcinogenesis and tumor progression

Fang, J. S., Gillies, R. D., & Gatenby, R. A. (2008) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2008.03.011 · Cited by 284

Overexpression of hypoxia-inducible factor HIF-1α predicts early relapse in breast cancer: Retrospective study in a series of 745 patients

Dalès, J.-P., Garcia, S., Meunier-Carpentier, S., Andrac, L., Haddad, O., Lavaut, M., Allasia, C., Bonnier, P., & Charpin, C. (2005) · International Journal of Cancer · doi:10.1002/ijc.20984 · Cited by 263

Targeting hypoxia cell signaling for cancer therapy

Melillo, G. (2007) · Cancer and Metastasis Reviews · doi:10.1007/s10555-007-9059-x · Cited by 230

Differential prognostic impact of hypoxia induced and diffuse HIF-1α expression in invasive breast cancer

Vleugel, M. M., Greijer, A. E., Shvarts, A., van der Groep, P., van Berkel, M., Aarbodem, Y., van Tinteren, H., Harris, A. L., van Diest, P. J., & van der Wall, E. (2005) · Journal of Clinical Pathology · doi:10.1136/jcp.2004.019885 · Cited by 227

Hypoxia-Inducible Factor 1? Expression Correlates with Angiogenesis and Unfavorable Prognosis in Bladder Cancer

Theodoropoulos, V. (2004) · European Urology · doi:10.1016/j.eururo.2004.04.008 · Cited by 223

Lactate Dehydrogenase 5 Expression in Operable Colorectal Cancer: Strong Association With Survival and Activated Vascular Endothelial Growth Factor Pathway—A Report of the Tumour Angiogenesis Research Group

Koukourakis, M. I., Giatromanolaki, A. N., Sivridis, E., Gatter, K. C., & Harris, A. L. (2006) · Journal of Clinical Oncology · doi:10.1200/jco.2006.05.9501 · Cited by 221

Association of hypoxia‐inducible factors 1α and 2α with activated angiogenic pathways and prognosis in patients with endometrial carcinoma

Sivridis, E., Giatromanolaki, A., Gatter, K. C., Harris, A. L., Koukourakis, M. I., & for the Tumor and Angiogenesis Research Group (2002) · Cancer · doi:10.1002/cncr.10774 · Cited by 218

OS-9 Interacts with Hypoxia-Inducible Factor 1α and Prolyl Hydroxylases to Promote Oxygen-Dependent Degradation of HIF-1α

Baek, J. H., Mahon, P. C., Oh, J. C., Kelly, B., Krishnamachary, B., Pearson, M., Chan, D. A., Giaccia, A. J., & Semenza, G. L. (2005) · Molecular Cell · doi:10.1016/j.molcel.2005.01.011 · Cited by 218

Metabolic targeting of hypoxia and HIF1 in solid tumors can enhance cytotoxic chemotherapy

Cairns, R. A., Papandreou, I., Sutphin, P. D., & Denko, N. C. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0611662104 · Cited by 183

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Hypoxia-inducible factors 1?? and 2?? are related to vascular endothelial growth factor expression and a poorer prognosis in nodular malignant melanomas of the skin

Giatromanolaki, A. N., Sivridis, E., Kouskoukis, C., Gatter, K. C., Harris, A. L., & Koukourakis, M. I. (2003) · Melanoma Research · doi:10.1097/00008390-200310000-00008 · Cited by 155

Expression of hypoxia-inducible factor-1 alpha and associated proteins in pancreatic ductal adenocarcinoma and their impact on prognosis

Sun, H., Qiu, Z., Liu, J., Sun, J., Jiang, T., Huang, K., Yao, M., & Huang, C. L. (2007) · International Journal of Oncology · doi:10.3892/ijo.30.6.1359 · Cited by 129

Significant correlation of hypoxia-inducible factor-1α with treatment outcome in cervical cancer treated with radical radiotherapy

Burri, P., Djonov, V., Aebersold, D. M., Lindel, K., Studer, U., Altermatt, H. J., Mazzucchelli, L., Greiner, R. H., & Gruber, G. (2003) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/s0360-3016(02)04579-0 · Cited by 124

Hypoxia-inducible factor-1α expression in the gastric carcinogenesis sequence and its prognostic role in gastric and gastro-oesophageal adenocarcinomas

Griffiths, E. A., Pritchard, S. A., Valentine, H. R., Whitchelo, N., Bishop, P. W., Ebert, M., Price, P., Welch, I., & West, C. (2006) · British Journal of Cancer · doi:10.1038/sj.bjc.6603524 · Cited by 107

Lung cancer: An organized cellular and metabolic domain

Koukourakis, M. I., Giatromanolaki, A. N., Bougioukas, G., & Sivridis, E. (2007) · Cancer Biology & Therapy · doi:10.4161/cbt.6.9.4635 · Cited by 100

Hypoxia‐inducible factor 1α/vascular endothelial growth factor axis in astrocytomas. Associations with microvessel morphometry, proliferation and prognosis

Korkolopoulou, P. A., Patsouris, E., Konstantinidou, A. E., Pavlopoulos, P. M., Kavantzas, N., Boviatsis, E. I., Thymara, I., Perdiki, Μ., Thomas-Tsagli, E., Angelidakis, D., et al. (2004) · Neuropathology and Applied Neurobiology · doi:10.1111/j.1365-2990.2003.00535.x · Cited by 95

Evaluation of hypoxia‐inducible factor 1α overexpression as a predictor of tumour recurrence and progression in superficial urothelial bladder carcinoma

Theodoropoulos, V., Lazaris, A. C., Kastriotis, I., Spiliadi, C., Theodoropoulos, G. E., Tsoukala, V. K., Patsouris, E., & Sofras, F. A. (2005) · British Journal of Urology · doi:10.1111/j.1464-410x.2005.05314.x · Cited by 80

Hypoxia-inducible factor-1α expression and angiogenesis in gastrointestinal stromal tumor of the stomach

Takahashi, R., Tanaka, S., Hiyama, T., Ito, M., Kitadai, Y., Sumii, M., Haruma, K., & Chayama, K. (2003) · Oncology Reports · doi:10.3892/or.10.4.797 · Cited by 78

Spermidine/Spermine-N1-Acetyltransferase 2 Is an Essential Component of the Ubiquitin Ligase Complex That Regulates Hypoxia-inducible Factor 1α

Baek, J. H., Liu, Y. V., McDonald, K. R., Wesley, J. B., Hubbi, M. E., Byun, H., & Semenza, G. L. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m703504200 · Cited by 65

Metastatic cancer cells from c-erbB-2 negative primary breast cancer maintain the original c-erbB-2/HIF1α phenotype

Giatromanolaki, A. N., Koukourakis, M. I., Simopoulos, C., & Sivridis, E. (2007) · Cancer Biology & Therapy · doi:10.4161/cbt.6.2.3620 · Cited by 4

Hypoxia‐inducible factor‐1α in non small cell lung cancer: Relation to growth factor, protease and apoptosis pathways

Swinson, D. E. B., Jones, J. L., Cox, G., Richardson, D., Harris, A. L., & O'Byrne, K. J. (2004) · International Journal of Cancer · doi:10.1002/ijc.20052

Regulation of cancer cell metabolism

Cairns, R. A., Harris, I. S., & Mak, T. W. (2011) · Nature Reviews Cancer · doi:10.1038/nrc2981 · Cited by 4,744

Defining the role of hypoxia-inducible factor 1 in cancer biology and therapeutics

Semenza, G. L. (2010) · Oncogene · doi:10.1038/onc.2009.441 · Cited by 1,712

Mitochondrial ROS in cancer: initiators, amplifiers or an Achilles' heel?

Sabharwal, S. S., & Schumacker, P. T. (2014) · Nature reviews. Cancer · doi:10.1038/nrc3803 · Cited by 1,681

Role of the tumor microenvironment in PD-L1/PD-1-mediated tumor immune escape

Jiang, X., Wang, J., Deng, X., Xiong, F., Ge, J., Xiang, B., Wu, X., Ma, J., Zhou, M., Li, X., et al. (2019) · Molecular Cancer · doi:10.1186/s12943-018-0928-4 · Cited by 1,482

HIF-1 mediates metabolic responses to intratumoral hypoxia and oncogenic mutations

Semenza, G. L. (2013) · Journal of Clinical Investigation · doi:10.1172/jci67230 · Cited by 1,335

HIF-1 mediates metabolic responses to intratumoral hypoxia and oncogenic mutations

Semenza, G. L. (2013) · Journal of Clinical Investigation · doi:10.1172/jci67230 · Cited by 1,335

Therapeutic Targeting Hypoxia-Inducible Factor (HIF-1) in Cancer: Cutting Gordian Knot of Cancer Cell Metabolism

Sharma, A., Sinha, S., & Shrivastava, N. (2022) · Frontiers in Genetics · doi:10.3389/fgene.2022.849040 · Cited by 85

Regulation of Hypoxia Dependent Reprogramming of Cancer Metabolism: Role of HIF-1 and Its Potential Therapeutic Implications in Leukemia

Pandey, S., Singh, R., Habib, N., Tripathi, R., Kushwaha, R., & Mahdi, A. A. (2024) · Asian Pacific Journal of Cancer Prevention · doi:10.31557/apjcp.2024.25.4.1121 · Cited by 11

HIF-1-regulated glucose metabolism in the control of apoptosis signaling

Fulda, S. (2008) · Expert Review of Endocrinology & Metabolism · doi:10.1586/17446651.3.3.303 · Cited by 3

HIF-1: upstream and downstream of cancer metabolism

Semenza, G. L. (2009) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2009.10.009 · Cited by 1,431