Hypoxia and energetic tumour metabolism

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 glycolys...

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Bibliographic Details
Published in:Current opinion in genetics & development 2011-02, Vol.21 (1), p.67-72
Main Authors: Brahimi-Horn, M Christiane, Bellot, Gregory, Pouysségur, Jacques
Format: Article
Language:English
Subjects:
Cell Hypoxia
Cell Survival
Development Biology
Energy Metabolism
Humans
Hypoxia-Inducible Factor 1 - metabolism
Life Sciences
Medical Education
Neoplasms - metabolism
Neoplasms - pathology
Neoplasms - therapy
Stress, Physiological
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Summary: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.
ISSN:0959-437X
1879-0380
DOI:10.1016/j.gde.2010.10.006