title: Cancer cells incorporate and remodel exogenous palmitate into structural and oncogenic signaling lipids.
abstract: De novo lipogenesis is considered the primary source of fatty acids for lipid synthesis in cancer cells, even in the presence of exogenous fatty acids. Here, we have used an isotopic fatty acid labeling strategy coupled with metabolomic profiling platforms to comprehensively map palmitic acid incorporation into complex lipids in cancer cells. We show that cancer cells and tumors robustly incorporate and remodel exogenous palmitate into structural and oncogenic glycerophospholipids, sphingolipids, and ether lipids. We also find that fatty acid incorporation into oxidative pathways is reduced in aggressive human cancer cells, and instead shunted into pathways for generating structural and signaling lipids. Our results demonstrate that cancer cells do not solely rely on de novo lipogenesis, but also utilize exogenous fatty acids for generating lipids required for proliferation and protumorigenic lipid signaling. This article is part of a special issue entitled Lipid Metabolism in Cancer.
authors.affiliation: Program in Metabolic Biology, Department of Nutritional Sciences and Toxicology, University of California, Berkeley, Berkeley, CA 94720.
authors.forename: Sharon M
authors.initials: SM
authors.lastname: Louie
authors.affiliation: Program in Metabolic Biology, Department of Nutritional Sciences and Toxicology, University of California, Berkeley, Berkeley, CA 94720.
authors.forename: Lindsay S
authors.initials: LS
authors.lastname: Roberts
authors.affiliation: Program in Metabolic Biology, Department of Nutritional Sciences and Toxicology, University of California, Berkeley, Berkeley, CA 94720.
authors.forename: Melinda M
authors.initials: MM
authors.lastname: Mulvihill
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720.
authors.forename: Kunxin
authors.initials: K
authors.lastname: Luo
authors.affiliation: Program in Metabolic Biology, Department of Nutritional Sciences and Toxicology, University of California, Berkeley, Berkeley, CA 94720.
authors.forename: Daniel K
authors.initials: DK
authors.lastname: Nomura
mesh_terms: D045744:Cell Line, Tumor; D006801:Humans; D050356:Lipid Metabolism; D055432:Metabolomics; D015394:Molecular Structure; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D009857:Oncogenes; D019308:Palmitic Acid / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D019308:Palmitic Acid
keywords: AC; C1P; CPT; Cancer metabolism; Ceramide-1-phosphate; DAGs; EMT; FFA; Free fatty acid; LPA; LPC; LPE; Lipid signaling; Lysophosphatidic acid; MAGL; Metabolomics; PA; PAF; PC; PE; PEG; PG; PI; PS; Platelet activating factor; QQQ-LC/MS; SM; SRM; TAG; acyl carnitines; carnitine palmitoyl transferase; ceramide-1-phosphate; diacylglycerols; epithelial-to-mesenchymal transition; lysophosphatidic acids; lysophosphatidyl cholines; lysophosphatidyl ethanolamines; monoacylglycerol lipase; phosphatidic acids; phosphatidyl ethanolamines; phosphatidyl glycerols; phosphatidyl inositols; phosphatidyl serines; phospholipids such as phosphatidyl cholines; platelet activating factor; polyethylene glycol; single reaction monitoring; sphingomyelin; triacylglycerols; triple quadrupole liquid chromatography-mass spectrometry