Hepatocyte-specific knockout of the essential autophagy gene Autophagy-related 7 (Atg7) is sufficient to cause hepatic carcinogenesis. A recent paper by Lee et al. unveils the molecular pathway accounting for hepatic hypertrophy and hyperplasia followed by malignant transformation. This pathway involves the overactivation of the transcription factor yes-associated protein (YAP), which turns out to be an autophagic substrate. Of note, the transcriptional signature activated in mouse hepatocytes lacking Atg7 resembles that found in non-alcoholic steatohepatitis (NASH), as well as in the steatohepatitic subtype of human hepatocellular carcinomas.
Sayaka Inokuchi‐Shimizu, Eek Joong Park, Yoon Seok Roh, Ling Yang, Bi Zhang, Jingyi Song, Shuang Liang, Michael Pimienta, Koji Taniguchi, Xuefeng Wu, Kinji Asahina, William Lagakos, Mason R. Mackey, Akira Shizuo, Mark H. Ellisman, Dorothy D. Sears, Jerrold M. Olefsky, Michael Karin, David A. Brenner, Ekihiro Seki
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