Autophagy-deficient mice develop multiple liver tumors

A Takamura, M Komatsu, T Hara… - Genes & …, 2011 - genesdev.cshlp.org
A Takamura, M Komatsu, T Hara, A Sakamoto, C Kishi, S Waguri, Y Eishi, O Hino, K Tanaka
Genes & development, 2011genesdev.cshlp.org
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 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.
genesdev.cshlp.org