Browsing by Subject "acetyl-CoA synthetase"

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    Glucose-independent Acetate Metabolism Promotes Melanoma Cell Survival and Tumor Growth
    (American Society for Biochemistry and Molecular Biology, 2016-10-14) Lakhter, Alexander J.; Hamilton, James; Konger, Raymond L.; Brustovetsky, Nickolay; Broxmeyer, Hal E.; Naidu, Samisubbu R.; Microbiology and Immunology, School of Medicine
    Tumors rely on multiple nutrients to meet cellular bioenergetics and macromolecular synthesis demands of rapidly dividing cells. Although the role of glucose and glutamine in cancer metabolism is well understood, the relative contribution of acetate metabolism remains to be clarified. We show that glutamine supplementation is not sufficient to prevent loss of cell viability in a subset of glucose-deprived melanoma cells, but synergizes with acetate to support cell survival. Glucose-deprived melanoma cells depend on both oxidative phosphorylation and acetate metabolism for cell survival. Acetate supplementation significantly contributed to maintenance of ATP levels in glucose-starved cells. Unlike acetate, short chain fatty acids such as butyrate and propionate failed to prevent loss of cell viability from glucose deprivation. In vivo studies revealed that in addition to nucleo-cytoplasmic acetate assimilating enzyme ACSS2, mitochondrial ACSS1 was critical for melanoma tumor growth in mice. Our data indicate that acetate metabolism may be a potential therapeutic target for BRAF mutant melanoma.