Actuality of Warburg's views in our understanding of renal cancer metabolism.
More than 50 years ago, Warburg proposed that the shift in glucose metabolism from oxidative phosphorylation (OXPHOS) to glycolysis occurring in spite of an adequate oxygen supply was at the root of cancer. This hypothesis often disregarded over the following years has recently stirred up much interest due to progress made in cancer genetics and proteomics. Studies related to renal cancers have been particularly informative to understand how abnormal use of glucose and decrease in OXPHOS are linked to cell proliferation in tumors. Indeed, in aggressive tumors such as clear cell renal carcinoma, the von Hippel-Lindau factor invalidation stabilizes the hypoxia-inducible factor (HIF) in the presence of oxygen. HIF stimulating glycolytic gene expression increases the glycolytic flux. Deficiencies in genes involved in oxidative phosphorylation that can explain the down-regulation of OXPHOS components also begin to be identified. These findings are important in the search for novel therapeutic approaches to cancer treatment.
Godinot
Catherine
C
Center of Molecular and Cellular Genetics (CGMC), UMR 5534, CNRS, University Claude Bernard of Lyon 1, 69622 Villeurbanne, France. godinot1@yahoo.com
de Laplanche
Elodie
E
Hervouet
Eric
E
Simonnet
Hélène
H
D000818:Animals; D002292:Carcinoma, Renal Cell / Q000378:metabolism*; D006019:Glycolysis; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000378:metabolism; D007680:Kidney Neoplasms / Q000378:metabolism*; D008928:Mitochondria / Q000502:physiology*; D010085:Oxidative Phosphorylation; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000378:metabolism
D051793:Hypoxia-Inducible Factor 1; D051794:Von Hippel-Lindau Tumor Suppressor Protein