Understanding the central role of citrate in the metabolism of cancer cells

Cancers cells strongly stimulate glycolysis and glutaminolysis for their biosynthesis. Pyruvate derived from glucose is preferentially diverted towards the production of lactic acid (Warburg effect). Citrate censors ATP production and controls strategic enzymes of anabolic and catabolic pathways thr...

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Bibliographic Details
Published in:Biochimica et biophysica acta 2012, Vol.1825 (1), p.111-116
Main Authors: Icard, Philippe, Poulain, Laurent, Lincet, Hubert
Format: Article
Language:English
Subjects:
Adaptative metabolism
Cancer
Cell Proliferation
Citrate
Citric Acid - metabolism
Glycolysis
Humans
Neoplasms - metabolism
Vicious cycle
Warburg
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Summary:Cancers cells strongly stimulate glycolysis and glutaminolysis for their biosynthesis. Pyruvate derived from glucose is preferentially diverted towards the production of lactic acid (Warburg effect). Citrate censors ATP production and controls strategic enzymes of anabolic and catabolic pathways through feedback reactions. Mitochondrial citrate diffuses in the cytosol to restore oxaloacetate and acetyl-CoA. Whereas acetyl-CoA serves de novo lipid synthesis and histone acetylation, OAA is derived towards lactate production via pyruvate and / or a vicious cycle reforming mitochondrial citrate. This cycle allows cancer cells to burn their host's lipid and protein reserves in order to sustain their own biosynthesis pathways. In vitro, citrate has demonstrated anti-cancer properties when administered in excess, sensitizing cancer cells to chemotherapy. Understanding its central role is of particular relevance for the development of new strategies for counteracting cancer cell proliferation and overcoming chemoresistance.
ISSN:0304-419X
0006-3002
1879-2561
DOI:10.1016/j.bbcan.2011.10.007