Oncogene KRAS activates fatty acid synthase, resulting in specific ERK and lipid signatures associated with lung adenocarcinoma
Abstract
We studied lung tumors induced by oncogene KRAS gene mutation using transgenic mice and human lung specimens. Gene expression analyses show that KRAS induces fatty acid synthase (FASN), promoting lipogenesis. Through desorption electrospray ionization MS imaging, we found specific lipid modifications in KRAS lung adenocarcinoma. Nanoimmunoassay identified specific KRAS-associated phosphoprotein signatures. We showed that KRAS activates the ERK2 protein, whereas non-KRAS lung adenocarcinoma shows elevated ERK1. We inhibited FASN by a small molecule, cerulenin, and this inhibition blocked cellular proliferation of KRAS-driven lung cancer cells. FASN inhibitors may, thus, present promising therapeutic agents for the treatment of KRAS-associated lung adenocarcinoma.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Apr 11, 2017
- Source ID
- 10.1073/pnas.1617709114
Entities
People
- Arvin M. Gouw
- Dean W Felsher
- Delaney K. Sullivan
- Georgia G. Toal
- Katherine Margulis
- Ling Tong
- Livia S. Eberlin
- Richard Zare
Organizations
- Air Force Office of Scientific Research
- National Institutes of Health
- Stanford University
- University of Texas at Austin