title: Oncogene KRAS activates fatty acid synthase, resulting in specific ERK and lipid signatures associated with lung adenocarcinoma.
abstract: KRAS gene mutation causes lung adenocarcinoma. KRAS activation has been associated with altered glucose and glutamine metabolism. Here, we show that KRAS activates lipogenesis, and this activation results in distinct proteomic and lipid signatures. By gene expression analysis, KRAS is shown to be associated with a lipogenesis gene signature and specific induction of fatty acid synthase (FASN). Through desorption electrospray ionization MS imaging (DESI-MSI), specific changes in lipogenesis and specific lipids are identified. By the nanoimmunoassay (NIA), KRAS is found to activate the protein ERK2, whereas ERK1 activation is found in non-KRAS-associated human lung tumors. The inhibition of FASN by cerulenin, a small molecule antibiotic, blocked cellular proliferation of KRAS-associated lung cancer cells. Hence, KRAS is associated with activation of ERK2, induction of FASN, and promotion of lipogenesis. FASN may be a unique target for KRAS-associated lung adenocarcinoma remediation.
authors.affiliation: Division of Oncology, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305.|Division of Oncology, Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305.
authors.forename: Arvin M
authors.initials: AM
authors.lastname: Gouw
authors.affiliation: Department of Chemistry, Stanford University, Stanford, CA 94305.|Department of Chemistry, The University of Texas at Austin, Austin, TX 78712.
authors.forename: Livia S
authors.initials: LS
authors.lastname: Eberlin
authors.affiliation: Department of Chemistry, Stanford University, Stanford, CA 94305.
authors.forename: Katherine
authors.initials: K
authors.lastname: Margulis
authors.affiliation: Division of Oncology, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305.|Division of Oncology, Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305.
authors.forename: Delaney K
authors.initials: DK
authors.lastname: Sullivan
authors.affiliation: Division of Oncology, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305.|Division of Oncology, Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305.
authors.forename: Georgia G
authors.initials: GG
authors.lastname: Toal
authors.affiliation: Division of Oncology, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305.|Division of Oncology, Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305.
authors.forename: Ling
authors.initials: L
authors.lastname: Tong
authors.affiliation: Department of Chemistry, Stanford University, Stanford, CA 94305; zare@stanford.edu dfelsher@stanford.edu.
authors.forename: Richard N
authors.initials: RN
authors.lastname: Zare
authors.affiliation: Division of Oncology, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305; zare@stanford.edu dfelsher@stanford.edu.|Division of Oncology, Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305.
authors.forename: Dean W
authors.initials: DW
authors.lastname: Felsher
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D000077192:Adenocarcinoma of Lung; D064429:Fatty Acid Synthases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D050356:Lipid Metabolism; D050155:Lipogenesis; D008175:Lung Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
chemical_list: C117307:KRAS protein, human; D064429:Fatty Acid Synthases; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D016283:Proto-Oncogene Proteins p21(ras)
keywords: KRAS; MS; fatty acid synthase; lipogenesis; lung