Regulation of cancer cell metabolism by hypoxia-inducible factor 1

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

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.

Publication types

  • Review

MeSH terms

  • Animals
  • Cell Hypoxia / physiology*
  • Gene Expression Regulation, Neoplastic
  • Glycolysis / physiology
  • Humans
  • Hypoxia-Inducible Factor 1 / genetics
  • Hypoxia-Inducible Factor 1 / metabolism*
  • Metabolic Networks and Pathways / physiology*
  • Neoplasms / enzymology
  • Neoplasms / genetics
  • Neoplasms / metabolism*
  • Reactive Oxygen Species / metabolism
  • Von Hippel-Lindau Tumor Suppressor Protein / metabolism*

Substances

  • Hypoxia-Inducible Factor 1
  • Reactive Oxygen Species
  • Von Hippel-Lindau Tumor Suppressor Protein