The reduced concentration of citrate in cancer cells: An indicator of cancer aggressiveness and a possible therapeutic target

Abstract : Proliferating cells reduce their oxidative metabolism and rely more on glycolysis, even in the presence of O 2 (Warburg effect). This shift in metabolism reduces citrate biosynthesis and diminishes intracellular acidity, both of which promote glycolysis sustaining tumor growth. Because citrate is the donor of acetyl-CoA, its reduced production favors a deacetylation state of proteins favoring resistance to apoptosis and epigenetic changes, both processes contributing to tumor aggressiveness. Citrate levels could be monitored as an indicator of cancer aggressiveness (as already shown in human prostate cancer) and/or could serve as a biomarker for response to therapy. Strategies aiming to increase cytosolic citrate should be developed and tested in humans, knowing that experimental studies have shown that administration of citrate and/or inhibition of ACLY arrest tumor growth, inhibit the expression of the key anti-apoptotic factor Mcl-1, reverse cell dedifferentiation and increase sensibility to cisplatin.
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Drug Resistance Updates, Elsevier, 2016, 29, pp.47 - 53. 〈10.1016/j.drup.2016.09.003〉
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Soumis le : jeudi 5 janvier 2017 - 12:51:14
Dernière modification le : jeudi 8 février 2018 - 11:10:18
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Icard Philippe, Lincet Hubert. The reduced concentration of citrate in cancer cells: An indicator of cancer aggressiveness and a possible therapeutic target. Drug Resistance Updates, Elsevier, 2016, 29, pp.47 - 53. 〈10.1016/j.drup.2016.09.003〉. 〈inserm-01427151〉

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