HIF-1 mediates metabolic responses to intratumoral hypoxia and oncogenic mutations.

Abstract

Hypoxia occurs frequently in human cancers and induces adaptive changes in cell metabolism that include a switch from oxidative phosphorylation to glycolysis, increased glycogen synthesis, and a switch from glucose to glutamine as the major substrate for fatty acid synthesis. This broad metabolic reprogramming is coordinated at the transcriptional level by HIF-1, which functions as a master regulator to balance oxygen supply and demand. HIF-1 is also activated in cancer cells by tumor suppressor (e.g., VHL) loss of function and oncogene gain of function (leading to PI3K/AKT/mTOR activity) and mediates metabolic alterations that drive cancer progression and resistance to therapy. Inhibitors of HIF-1 or metabolic enzymes may impair the metabolic flexibility of cancer cells and make them more sensitive to anticancer drugs.

• Authors: Gregg L Semenza
• Journal: The Journal of clinical investigation (J Clin Invest) Vol. 123 Issue 9 Pg. 3664-71 (Sep 2013) ISSN: 1558-8238 [Electronic] United States
• PMID: 23999440 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Review)

Chemical References

• HIF1A protein, human
• Hypoxia-Inducible Factor 1, alpha Subunit

Topics

• Adaptation, Physiological
• Animals
• Cell Hypoxia
• Drug Resistance, Neoplasm
• Energy Metabolism
• Humans
• Hypoxia-Inducible Factor 1, alpha Subunit (physiology)
• Mutation
• Neoplasms (drug therapy, genetics, metabolism, pathology)
• Oncogenes