Department of Physiology and Cell Biology, Tokyo Medical and Dental University, Tokyo 113-8519, Japan.
Genes Dev. 2011 Apr 15;25(8):795-800. doi: 10.1101/gad.2016211.
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.
自噬是细胞质蛋白和细胞器降解的主要途径，已被牵连到肿瘤抑制中。在这里，我们报告说，Atg5 全身嵌合缺失和肝脏特异性 Atg7⁻/⁻的小鼠会发展出良性肝腺瘤。这些肿瘤细胞起源于自噬缺陷的肝细胞，并表现出线粒体肿胀、p62 积累以及氧化应激和基因组损伤反应。同时删除 p62 会减小 Atg7⁻/⁻肝脏肿瘤的大小。这些结果表明，自噬通过一种细胞内在的机制对于抑制自发性肿瘤发生非常重要，特别是在肝脏中，并且 p62 的积累有助于肿瘤的进展。
