Oncogenic KRAS Induces NIX-Mediated Mitophagy to Promote Pancreatic Cancer.

ABSTRACT: Activating KRAS mutations are found in nearly all cases of pancreatic ductal adenocarcinoma (PDAC), yet effective clinical targeting of oncogenic KRAS remains elusive. Understanding of KRAS-dependent PDAC-promoting pathways could lead to the identification of vulnerabilities and the development of new treatments. We show that oncogenic KRAS induces BNIP3L/NIX expression and a selective mitophagy program that restricts glucose flux to the mitochondria and enhances redox capacity. Loss of Nix restores functional mitochondria to cells, increasing demands for NADPH reducing power and decreasing proliferation in glucose-limited conditions. Nix deletion markedly delays progression of pancreatic cancer and improves survival in a murine (KPC) model of PDAC. Altho

SUBMITTER: Humpton TJ 

PROVIDER: S-EPMC6726540 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature