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Cited by 837

The DOI matches its Crossref record; 5 of the 5 references it cites were found in a registry or an index.

Hypoxia-inducible Factor 1 Activation by Aerobic Glycolysis Implicates the Warburg Effect in Carcinogenesis

Open access
Lu, Huasheng, Forbes, Robert A., Verma, Ajay·2002·Journal of Biological Chemistry

Abstract

Cancer cells display high rates of aerobic glycolysis, a phenomenon known historically as the Warburg effect. Lactate and pyruvate, the end products of glycolysis, are highly produced by cancer cells even in the presence of oxygen. Hypoxia-induced gene expression in cancer cells has been linked to malignant transformation. Here we provide evidence that lactate and pyruvate regulate hypoxia-inducible gene expression independently of hypoxia by stimulating the accumulation of hypoxia-inducible Factor 1alpha (HIF-1alpha). In human gliomas and other cancer cell lines, the accumulation of HIF-1alpha protein under aerobic conditions requires the metabolism of glucose to pyruvate that prevents the aerobic degradation of HIF-1alpha protein, activates HIF-1 DNA binding activity, and enhances the expression of several HIF-1-activated genes including erythropoietin, vascular endothelial growth factor, glucose transporter 3, and aldolase A. Our findings support a novel role for pyruvate in metabolic signaling and suggest a mechanism by which high rates of aerobic glycolysis can promote the malignant transformation and survival of cancer cells.

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Metadata

Authors
Lu, H., Forbes, R. A., & Verma, A.
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2002-06
Volume
277
Issue
26
Pages
23111-23115
ISSN
0021-9258 (ISSN-L)
OpenAlex
W2060628991
Cited by
837
References
5
FWCI
6.33
Type
journal article
Language
en
Open access
hybrid

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CoChat. (2026). Citation check: Hypoxia-inducible Factor 1 Activation by Aerobic Glycolysis Implicates the Warburg Effect in Carcinogenesis. https://app.cochat.ai/papers/10.1074/jbc.m202487200
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Lu, H., Forbes, R. A., & Verma, A. (2002). Hypoxia-inducible Factor 1 Activation by Aerobic Glycolysis Implicates the Warburg Effect in Carcinogenesis. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m202487200

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