Regulation of cancer cell metabolism by hypoxia-inducible factor 1.
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.
Semenza
Gregg L
GL
Institute for Cell Engineering, Department of Pediatrics, McKusick-Nathans Institute of Genetic Medicine, The Johns Hopkins University School of Medicine, United States. gsemenza@jhmi.edu
D000818:Animals; D015687:Cell Hypoxia / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic; D006019:Glycolysis / Q000502:physiology; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000235:genetics / Q000378:metabolism*; D053858:Metabolic Networks and Pathways / Q000502:physiology*; D009369:Neoplasms / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000378:metabolism*
D051793:Hypoxia-Inducible Factor 1; D017382:Reactive Oxygen Species; D051794:Von Hippel-Lindau Tumor Suppressor Protein