De novo lipogenesis represents a therapeutic target in mutant Kras non-small cell lung cancer.

ABSTRACT: Oncogenic Kras mutations are one of the most common alterations in non-small cell lung cancer and are associated with poor response to treatment and reduced survival. Driver oncogenes, such as Kras are now appreciated for their ability to promote tumor growth via up-regulation of anabolic pathways. Therefore, we wanted to identify metabolic vulnerabilities in Kras-mutant lung cancer. Using the Kras ^LSL-G12D lung cancer model, we show that mutant Kras drives a lipogenic gene-expression program. Stable-isotope analysis reveals that mutant Kras promotes de novo fatty acid synthesis in vitro and in vivo. The importance of fatty acid synthesis in Kras-induced tumorigenesis was evident by decreased tumor formation in Kras ^LSL-G12D mice after treatment with a fatty acid synt

SUBMITTER: Singh A 

PROVIDER: S-EPMC6219836 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature