Hypoxia signalling controls metabolic demand.
It has been known for quite some time that cancer cells undergo far-reaching modifications in their metabolism, yet a full understanding of these changes and how they come about remains elusive. Even under conditions of plentiful oxygen, cancer cells choose to switch glucose metabolism from respiration to lactic acid formation. The mystery behind the molecular mechanisms of this phenomenon, known as the Warburg effect, is now being unravelled. The reduced respiration rate and increased glucose uptake associated with lactic acid production, and acidosis of the micro-environment, are primarily due to activation of the alpha/beta hypoxia-inducible transcription factor. This distinctive metabolic nature of cancer cells is already being exploited as a diagnostic tool but is yet to be harnessed as a therapeutic intervention.
Brahimi-Horn
M Christiane
MC
Institute of Signaling, Developmental Biology and Cancer Research, CNRS UMR 6543, University of Nice, Centre A. Lacassagne, 33 Avenue Valombrose, 06189 Nice, France. brahimi@unice.fr
Chiche
Johanna
J
Pouysségur
Jacques
J
D000818:Animals; D015687:Cell Hypoxia; D006801:Humans; D006863:Hydrogen-Ion Concentration; D051793:Hypoxia-Inducible Factor 1 / Q000378:metabolism*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D019344:Lactic Acid / Q000378:metabolism; D008954:Models, Biological; D009369:Neoplasms / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D015398:Signal Transduction
D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D019344:Lactic Acid