Nf1 Loss Promotes Kras-Driven Lung Adenocarcinoma and Results in Psat1-Mediated Glutamate Dependence

ABSTRACT: Mutations to KRAS are recurrent in lung adenocarcinomas (LUAD) and are daunting to treat due to the difficulties in KRAS oncoprotein inhibition. A possible resolution to this problem may lie with co-mutations to other genes that also occur in KRAS¬-driven LUAD, that may provide alternative therapeutic vulnerabilities. Approximately 3% of KRAS-mutant LUADs carry functional mutations in NF1 gene encoding neurofibromin-1, a negative regulator of focal adhesion kinase 1 (FAK1). We evaluated the impact of Nf1 loss on LUAD development using a CRISPR/Cas9 platform in a murine model of Kras-mutant LUAD. We discovered that Nf1 deactivation is associated with Fak1 hyperactivation and phosphoserine aminotransferase 1 (Psat1) upregulation in mice. Nf1 loss also accelerates murine Kras-driven LUAD tumo

SUBMITTER: Xiaojing Wang 

PROVIDER: S-SCDT-EMM-2018-09856-T | biostudies-other |

REPOSITORIES: biostudies-other