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Semin Cancer Biol. 2009 Feb;19(1):12-6. doi: 10.1016/j.semcancer.2008.11.009. Epub 2008 Dec 9.

Regulation of cancer cell metabolism by hypoxia-inducible factor 1.

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  • 1Institute for Cell Engineering, Department of Pediatrics, McKusick-Nathans Institute of Genetic Medicine, The Johns Hopkins University School of Medicine, United States. gsemenza@jhmi.edu

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.

PMID:
19114105
[PubMed - indexed for MEDLINE]
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