The transcription factor HIF-1α plays a critical role in the growth factor-dependent regulation of both aerobic and anaerobic glycolysis
Open accessAbstract
Mammalian cells are believed to have a cell-intrinsic ability to increase glucose metabolism in response to hypoxia. Here we show that the ability of hematopoietic cells to up-regulate anaerobic glycolysis in response to hypoxia is dependent on receptor-mediated signal transduction. In the absence of growth factor signaling, hematopoietic cells fail to express hypoxia-inducible transcription factor (Hif-1 α) mRNA. Growth factor-deprived hematopoietic cells do not engage in glucose-dependent anabolic synthesis and neither express Hif-1 α mRNA nor require HIF-1α protein to regulate cell survival in response to hypoxia. However, HIF-1α is adaptive for the survival of growth factor-stimulated cells, as suppression of HIF-1α results in death when growing cells are exposed to hypoxia. Growth factor-dependent HIF-1α expression reprograms the intracellular fate of glucose, resulting in decreased glucose-dependent anabolic synthesis and increased lactate production, an effect that is enhanced when HIF-1α protein is stabilized by hypoxia. Together, these data suggest that HIF-1α contributes to the regulation of growth factor-stimulated glucose metabolism even in the absence of hypoxia.
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By diverting pyruvate into lactate, HIF-1 blocks glucose carbon incorporation into mitochondrial citrate which is critical for lipid synthesis.
“By diverting pyruvate into lactate, HIF-1 blocks glucose carbon incorporation into mitochondrial citrate which is critical for lipid synthesis (Lum et al., 2007).”
From Metabolic Reprogramming: A Cancer Hallmark Even Warburg Did Not Anticipate (2012) · cites this paper as Lum et al., 2007
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- Authors
- Lum, J. J., Bui, T., Gruber, M., Gordan, J. D., DeBerardinis, R. J., Covello, K. L., Simon, M. C., & Thompson, C. B.
- Affiliations
- University of Pennsylvania (US)
- Children's Hospital of Philadelphia (US)
- Howard Hughes Medical Institute (US)
- ORCID
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2007-04-16
- Volume
- 21
- Issue
- 9
- Pages
- 1037-1049
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- PMC
- PMC1855230
- OpenAlex
- W2118336842
- Cited by
- 429
- References
- 55
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- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes & Development (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Leukemia and Lymphoma Society
- National Institutes of Health
- National Cancer Institute
- 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
- Health Sciences › Medicine › Hematology › Erythropoietin and Anemia Treatment
- Keywords
- HIF-1α, hypoxia-inducible factor, aerobic glycolysis, anaerobic glycolysis, glucose metabolism, growth factor signaling, hematopoietic cells, cell survival, lactic acid production, hypoxia, receptor signaling
- MeSH terms
- Aerobiosis, Anaerobiosis, Animals, Base Sequence, Cell Line, Cell Survival, Glucose, Glycolysis, Growth Substances, Hematopoietic System, Interleukin-3, Mice, Mutant Strains, Models, Biological, RNA, Messenger, Signal Transduction, Cell Hypoxia, Gene Deletion, NIH 3T3 Cells, Cell Proliferation, Mice, Hypoxia-Inducible Factor 1, alpha Subunit
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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