The DOI matches its Crossref record; 66 of the 67 references it cites were found in a registry or an index.
Regulation of cancer cell metabolism by hypoxia-inducible factor 1
Abstract
The induction of hypoxia-inducible factor 1 (HIF-1) activity, either as a result of intratumoral hypoxia or loss-of-function mutations in the VHL gene, leads to a dramatic reprogramming of cancer cell metabolism involving increased glucose transport into the cell, increased conversion of glucose to pyruvate, and a concomitant decrease in mitochondrial metabolism and mitochondrial mass. Blocking these adaptive metabolic responses to hypoxia leads to cell death due to toxic levels of reactive oxygen species. Targeting HIF-1 or metabolic enzymes encoded by HIF-1 target genes may represent a novel therapeutic approach to cancer.
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“HIF-1α also activates metabolic genes, such as PGK-1 and PFK1A, which increase glycolysis for ATP production during hypoxia (Semenza, 2009).”
From SirT3 suppresses hypoxia inducible factor 1α and tumor growth by inhibiting mitochondrial ROS production (2011) · cites this paper as Semenza, 2009
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1 retracted
Mitochondrial Autophagy Is an HIF-1-dependent Adaptive Metabolic Response to Hypoxia
Zhang, H., Bosch-Marce, M., Shimoda, L. A., Tan, Y. S., Baek, J. H., Wesley, J. B., Gonzalez, F. J., & Semenza, G. L. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m800102200 · Cited by 1,601
Self-citationRetractedTargeting HIF-1 for cancer therapy
Semenza, G. L. (2003) · Nature Reviews Cancer · doi:10.1038/nrc1187 · Cited by 6,717
Self-citationWang, 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
Self-citationJaakkola, 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
Ivan, M., Kondo, K., Yang, H., Kim, W., Valiando, J., Ohh, M., Salic, A., Asara, J. M., Lane, W. S., & Kaelin Jr., W. G. (2001) · Science · doi:10.1126/science.1059817 · Cited by 4,735
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
Self-citationEpstein, 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
Ferrara, N., Hillan, K. J., Gerber, H.-P., & Novotny, W. (2004) · Nature Reviews Drug Discovery · doi:10.1038/nrd1381 · Cited by 2,625
Cellular and developmental control of O 2 homeostasis by hypoxia-inducible factor 1α
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) · Genes & Development · doi:10.1101/gad.12.2.149 · Cited by 2,476
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Cited by
Sorted by citations
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
Self-citationMitochondrial 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
Self-citation
Metadata
- Authors
- Semenza, G. L.
- Affiliations
- Johns Hopkins University (US)
- Corresponding author
- Semenza, Gregg L.
- ORCID
- Semenza, Gregg L.
- Venue
- Seminars in Cancer Biology
- Publisher
- Elsevier BV
- Published
- 2009-02
- Volume
- 19
- Issue
- 1
- Pages
- 12-16
- ISSN
- 1044-579X (ISSN-L)
- OpenAlex
- W2102416115
- Cited by
- 469
- References
- 67
- Citations by year
- 2026: 14 · 2025: 11 · 2024: 15 · 2023: 19 · 2022: 14 · 2021: 28 · 2020: 21 · 2019: 21 · 2018: 22 · 2017: 29 · 2016: 36 · 2015: 32 · 2014: 33 · 2013: 35 · 2012: 35
- FWCI
- 2.46
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Seminars in Cancer Biology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Keywords
- HIF-1, cancer metabolism, tumor hypoxia, VHL gene, glucose transport, glycolysis, mitochondrial metabolism, reactive oxygen species, HIF-1 target genes, metabolic reprogramming, cancer therapy
- MeSH terms
- Animals, Glycolysis, Humans, Neoplasms, Cell Hypoxia, Gene Expression Regulation, Neoplastic, Reactive Oxygen Species, Hypoxia-Inducible Factor 1, Von Hippel-Lindau Tumor Suppressor Protein, Metabolic Networks and Pathways
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