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Publication : Glycolytic cancer cells lacking 6-phosphogluconate dehydrogenase metabolize glucose to induce senescence.

First Author  Sukhatme VP Year  2012
Journal  FEBS Lett Volume  586
Issue  16 Pages  2389-95
PubMed ID  22677172 Mgi Jnum  J:187006
Mgi Id  MGI:5435114 Doi  10.1016/j.febslet.2012.05.052
Citation  Sukhatme VP, et al. (2012) Glycolytic cancer cells lacking 6-phosphogluconate dehydrogenase metabolize glucose to induce senescence. FEBS Lett 586(16):2389-95
abstractText  We show that knockdown of 6-phosphogluconate dehydrogenase (6PGD) of the pentose phosphate pathway (PPP) inhibits growth of lung cancer cells by senescence induction. This inhibition is not due to a defect in the oxidative PPP per se. NADPH and ribose phosphate production are normal in 6PGD knockdown cells and shutdown of PPP by knockdown of glucose-6-phosphate dehydrogenase (G6PD) has little effect on cell growth. Moreover, 6PGD knockdown cells can proliferate when the PPP is bypassed by using fructose instead of glucose in medium. Significantly, G6PD knockdown rescues proliferation of cells lacking 6PGD, suggesting an accumulation of growth inhibitory glucose metabolics in cells lacking 6PGD. Therefore, 6PGD inhibition may provide a novel strategy to treat glycolyic tumors such as lung cancer.
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