Autophagy-deficient mice develop multiple liver tumors

TLDR

Autophagy degrades cytoplasmic proteins and organelles and is implicated in tumor suppression. Mice lacking Atg5 or liver‑specific Atg7 develop benign liver adenomas from autophagy‑deficient hepatocytes, and p62 deletion reduces tumor size, showing autophagy suppresses liver tumorigenesis while p62 promotes progression.

Abstract

Autophagy is a major pathway for degradation of cytoplasmic proteins and organelles, and has been implicated in tumor suppression. Here, we report that mice with systemic mosaic deletion of Atg5 and liver-specific Atg7 −/− mice develop benign liver adenomas. These tumor cells originate autophagy-deficient hepatocytes and show mitochondrial swelling, p62 accumulation, and oxidative stress and genomic damage responses. The size of the Atg7 −/− liver tumors is reduced by simultaneous deletion of p62. These results suggest that autophagy is important for the suppression of spontaneous tumorigenesis through a cell-intrinsic mechanism, particularly in the liver, and that p62 accumulation contributes to tumor progression.