Hypoxia-Inducible Factor-1α and the Glycolytic Phenotype in Tumors
Open accessAbstract
Metastatic tumors generally exhibit aerobic glycolysis (the Warburg effect). The advent of [18F]fluorodeoxyglucose positron emission tomography imaging, coupled with recent findings linking hypoxia-inducible factor (HIF-1alpha) overexpression to aggressive cancers, has rekindled an interest in this aspect of tumor metabolism. These studies explore the role of HIF-1alpha in human breast cancer lines and its relationship to glycolytic regulation. Here we demonstrate that, under normal oxygen conditions, nonmetastatic cells consume less glucose and express low HIF-1alpha, whereas metastatic cells constitutively express high glycolysis and HIF-1alpha, suggesting that dysregulation of HIF-1alpha may induce the Warburg effect. This hypothesis was tested by renormalizing HIF-1alpha levels in renal carcinoma cells, leading to inhibition of aerobic glycolysis.
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HIF1α stabilization and elevated HIF1α protein levels are characteristic for ~50% of tumor cells under normoxia.
“It has been well-known since the early 2000s, that the HIF1α stabilization and the elevated HIF1α protein levels are characteristic for ∼50% of tumor cells under normoxia [35].”
From Hypoxia Signaling in Cancer: From Basics to Clinical Practice (2021) · cites this paper as [35]
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- Authors
- Robey, I. F., Lien, A. D., Welsh, S. J., Baggett, B. K., & Gillies, R. J.
- Affiliations
- University of Arizona Cancer Center (US)
- Corresponding author
- Gillies, Robert J.
- Venue
- Neoplasia
- Publisher
- Elsevier BV
- Published
- 2005-04
- Volume
- 7
- Issue
- 4
- Pages
- 324-330
- ISSN
- 1476-5586 (ISSN-L)
- PMC
- PMC1501147
- OpenAlex
- W2088715496
- Cited by
- 251
- References
- 45
- Citations by year
- 2026: 6 · 2025: 8 · 2024: 9 · 2023: 16 · 2022: 14 · 2021: 15 · 2020: 10 · 2019: 16 · 2018: 7 · 2017: 8 · 2016: 6 · 2015: 10 · 2014: 15 · 2013: 14 · 2012: 9
- FWCI
- 5.45
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Neoplasia (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- National Institutes of Health
- National Cancer Institute (R01-CA77575, R01CA077575, R01-CA77975-05)
- 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 › Cancer Research › Cancer, Lipids, and Metabolism
- Keywords
- hypoxia-inducible factor-1α, aerobic glycolysis, Warburg effect, cancer metabolism, metastasis, breast cancer cell lines, renal carcinoma cells, glucose utilization, glycolytic regulation, HIF-1α overexpression
- MeSH terms
- Hypoxia, Glucose, Glycolysis, Humans, Lactates, Neoplasms, Phenotype, Time Factors, Transcription Factors, Blotting, Western, Gene Expression Regulation, Neoplastic, DNA Primers, Reverse Transcriptase Polymerase Chain Reaction, Cell Line, Tumor, Hypoxia-Inducible Factor 1, alpha Subunit
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