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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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Mitochondrial Autophagy Is an HIF-1-dependent Adaptive Metabolic Response to Hypoxia
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The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis
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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
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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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