title: Acetate as a Metabolic and Epigenetic Modifier of Cancer Therapy.
abstract: Metabolic networks are significantly altered in neoplastic cells. This altered metabolic program leads to increased glycolysis and lipogenesis and decreased dependence on oxidative phosphorylation and oxygen consumption. Despite their limited mitochondrial respiration, cancer cells, nonetheless, derive sufficient energy from alternative carbon sources and metabolic pathways to maintain cell proliferation. They do so, in part, by utilizing fatty acids, amino acids, ketone bodies, and acetate, in addition to glucose. The alternative pathways used in the metabolism of these carbon sources provide opportunities for therapeutic manipulation. Acetate, in particular, has garnered increased attention in the context of cancer as both an epigenetic regulator of posttranslational protein modification, and as a carbon source for cancer cell biomass accumulation. However, to date, the data have not provided a clear understanding of the precise roles that protein acetylation and acetate oxidation play in carcinogenesis, cancer progression or treatment. This review highlights some of the major issues, discrepancies, and opportunities associated with the manipulation of acetate metabolism and acetylation-based signaling in cancer development and treatment.
authors.affiliation: Department of Neurological Sciences, University of Vermont College of Medicine, Burlington, Vermont.
authors.forename: Diane M
authors.initials: DM
authors.lastname: Jaworski
authors.affiliation: Department of Anatomy, Physiology and Genetics, Uniformed Services University of the Health Sciences, Bethesda, Maryland.
authors.forename: Aryan M A
authors.initials: AM
authors.lastname: Namboodiri
authors.affiliation: Department of Anatomy, Physiology and Genetics, Uniformed Services University of the Health Sciences, Bethesda, Maryland.
authors.forename: John R
authors.initials: JR
authors.lastname: Moffett
mesh_terms: D000106:Acetate-CoA Ligase / Q000502:physiology; D000085:Acetates / Q000378:metabolism; D000105:Acetyl Coenzyme A / Q000378:metabolism; D000107:Acetylation; D000818:Animals; D063646:Carcinogenesis / Q000378:metabolism; D044127:Epigenesis, Genetic; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000178:diet therapy / Q000188:drug therapy* / Q000201:enzymology; D011499:Protein Processing, Post-Translational; D015398:Signal Transduction
chemical_list: D000085:Acetates; D000105:Acetyl Coenzyme A; D000106:Acetate-CoA Ligase
keywords: ACETYL COENZYME A; ACETYL-CoA; ACETYL-CoA SYNTHETASE; ACETYLATION; DEACETYLATION; FATTY ACID; GLYCERYL TRIACETATE; KETOGENIC DIET; KETONE BODY; METABOLISM; REVIEW