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 language||American English|
|Number of pages||6|
|Journal||Proceedings of the National Academy of Sciences of the United States of America|
|State||Published - 25 Apr 2017|
Bibliographical noteFunding Information:
We thank Harold Varmus for the CCSP-rtTA/TetOKRAS4bG12D bitransgenic mice, and are grateful to Translational Applications Service Center at Stanford for the Nano Immuno Assay experiments. A.M.G. and K.M. acknowledge Stanford Cancer Translational Nanotechnology Training T32 Training Grant T32 CA196585 funded by the National Cancer Institute and the Stanford Center of Molecular Analysis and Design, respectively. This work is supported by NIH Grant R01CA184384.
- Fatty acid synthase