Autophagy suppresses Ras-driven epithelial tumourigenesis by limiting the accumulation of reactive oxygen species.

ABSTRACT: Activation of Ras signalling occurs in ~30% of human cancers; however, activated Ras alone is not sufficient for tumourigenesis. In a screen for tumour suppressors that cooperate with oncogenic Ras (Ras^V12) in Drosophila, we identified genes involved in the autophagy pathway. Bioinformatic analysis of human tumours revealed that several core autophagy genes, including GABARAP, correlate with oncogenic KRAS mutations and poor prognosis in human pancreatic cancer, supporting a potential tumour-suppressive effect of the pathway in Ras-driven human cancers. In Drosophila, we demonstrate that blocking autophagy at any step of the pathway enhances Ras^V12-driven epithelial tissue overgrowth via the accumulation of reactive oxygen species and activation of the Jun kinase stre

SUBMITTER: Manent J 

PROVIDER: S-EPMC5633656 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature