title: Hypoxia and energetic tumour metabolism.
abstract: The hypoxia-inducible factor (HIF-1), in addition to genetic and epigenetic changes, is largely responsible for alterations in cell metabolism in hypoxic tumour cells. This transcription factor not only favours cell proliferation through the metabolic shift from oxidative phosphorylation to glycolysis and lactic acid production but also stimulates nutrient supply by mediating adaptive survival mechanisms. These include epithelial-mesenchymal transition, angiogenesis, autophagy, and synthesis and storage of lipid and glycogen. HIF-1 also ensures survival by correcting tumour acidosis via increased expression of the carbonic anhydrase CA IX and the lactate/H+ symporter MCT4. The targeting of key HIF-1-mediated steps, responsible for exacerbated glycolysis and pHi-control, and of the 'guardian of cellular energy' AMP-kinase should offer novel therapeutic opportunities to fight cancer.
authors.affiliation: Institute of Developmental Biology and Cancer Research, University of Nice, CNRS UMR 6543, Centre A. Lacassagne, 33 Avenue Valombrose, 06189 Nice, France. brahimi@unice.fr
authors.forename: M Christiane
authors.initials: MC
authors.lastname: Brahimi-Horn
authors.forename: Gregory
authors.initials: G
authors.lastname: Bellot
authors.forename: Jacques
authors.initials: J
authors.lastname: Pouysségur
mesh_terms: D015687:Cell Hypoxia; D002470:Cell Survival; D004734:Energy Metabolism; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000378:metabolism; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D013312:Stress, Physiological
chemical_list: D051793:Hypoxia-Inducible Factor 1