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Proc Natl Acad Sci U S A. 2017 Apr 25;114(17):4300-4305. doi: 10.1073/pnas.1617709114. Epub 2017 Apr 11.

Oncogene KRAS activates fatty acid synthase, resulting in specific ERK and lipid signatures associated with lung adenocarcinoma.

Author information

1
Division of Oncology, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305.
2
Division of Oncology, Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305.
3
Department of Chemistry, Stanford University, Stanford, CA 94305.
4
Department of Chemistry, The University of Texas at Austin, Austin, TX 78712.
5
Department of Chemistry, Stanford University, Stanford, CA 94305; zare@stanford.edu dfelsher@stanford.edu.
6
Division of Oncology, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305; zare@stanford.edu dfelsher@stanford.edu.

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.

KEYWORDS:

KRAS; MS; fatty acid synthase; lipogenesis; lung

PMID:
28400509
PMCID:
PMC5410819
DOI:
10.1073/pnas.1617709114
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

Conflict of interest statement: The material in this manuscript is the subject of a provisional application to the United States Patent and Trademark Office.

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