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

Arvin M. Gouw, Livia S. Eberlin, Katherine Margulis, Delaney K. Sullivan, Georgia G. Toal, Ling Tong, Richard N. Zare, Dean W. Felsher

Research output: Contribution to journalArticlepeer-review

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 KRASassociated lung adenocarcinoma remediation.

Original languageAmerican English
Pages (from-to)4300-4305
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume114
Issue number17
DOIs
StatePublished - 25 Apr 2017
Externally publishedYes

Keywords

  • Fatty acid synthase
  • KRAS
  • Lipogenesis
  • Lung
  • MS

All Science Journal Classification (ASJC) codes

  • General

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