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Inhibiting Glutamine Utilization Creates A Synthetic Lethality For Suppression Of Atp Citrate Lyase In Kras-Driven Cancer Cells, Ahmet Hatipoglu, Deepak Menon, Talia Levy, Maria A. Frias, David A. Foster
Inhibiting Glutamine Utilization Creates A Synthetic Lethality For Suppression Of Atp Citrate Lyase In Kras-Driven Cancer Cells, Ahmet Hatipoglu, Deepak Menon, Talia Levy, Maria A. Frias, David A. Foster
Publications and Research
Metabolic reprogramming is now considered a hallmark of cancer cells. KRas-driven cancer cells use glutaminolysis to generate the tricarboxylic acid cycle intermediate α -ketoglutarate via a transamination reaction between glutamate and oxaloacetate. We reported previously that exogenously supplied unsaturated fatty acids could be used to synthesize phosphatidic acid–a lipid second messenger that activates both mammalian target of rapamycin (mTOR) complex 1 (mTORC1) and mTOR complex 2 (mTORC2). A key target of mTORC2 is Akt–a kinase that promotes survival and regulates cell metabolism. We report here that mono- unsaturated oleic acid stimulates the phosphoryla tion of ATP citrate lyase (ACLY) at …