Alterations of mTOR signaling impact metabolic stress resistance in colorectal carcinomas with BRAF and KRAS mutations.

ABSTRACT: Metabolic reprogramming is as a hallmark of cancer, and several studies have reported that BRAF and KRAS tumors may be accompanied by a deregulation of cellular metabolism. We investigated how BRAF^V600E and KRAS^G12V affect cell metabolism, stress resistance and signaling in colorectal carcinoma cells driven by these mutations. KRAS^G12V expressing cells are characterized by the induction of glycolysis, accumulation of lactic acid and sensitivity to glycolytic inhibition. Notably mathematical modelling confirmed the critical role of MCT1 designating the survival of KRAS^G12V cells. Carcinoma cells harboring BRAF^V600E remain resistant towards alterations of glucose supply or application of signaling or metabolic inhibitors. Altogether thes

SUBMITTER: Fritsche-Guenther R 

PROVIDER: S-EPMC6003911 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature