1. Academic Validation
  2. HIF-1: upstream and downstream of cancer metabolism

HIF-1: upstream and downstream of cancer metabolism

  • Curr Opin Genet Dev. 2010 Feb;20(1):51-6. doi: 10.1016/j.gde.2009.10.009.
Gregg L Semenza 1
Affiliations

Affiliation

  • 1 Vascular Program, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Broadway Research Building, Suite 671, 733 North Broadway, Baltimore, MD 21205, United States. [email protected]
Abstract

Hypoxia-inducible factor 1 (HIF-1) plays a key role in the reprogramming of Cancer metabolism by activating transcription of genes encoding glucose transporters and glycolytic Enzymes, which take up glucose and convert it to lactate; pyruvate dehydrogenase kinase 1, which shunts pyruvate away from the mitochondria; and BNIP3, which triggers selective mitochondrial Autophagy. The shift from oxidative to glycolytic metabolism allows maintenance of redox homeostasis and cell survival under conditions of prolonged hypoxia. Many metabolic abnormalities in Cancer cells increase HIF-1 activity. As a result, a feed-forward mechanism can be activated that drives HIF-1 activation and may promote tumor progression.

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