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

Significance 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.