p62, Upregulated during Preneoplasia, Induces Hepatocellular Carcinogenesis by Maintaining Survival of Stressed HCC-Initiating Cells

Atsushi Umemura, Feng He, Koji Taniguchi, Hayato Nakagawa, Shinichiro Yamachika, Joan Font-Burgada, Zhenyu Zhong, Shankar Subramaniam, Sindhu Raghunandan, Angeles Duran, Juan F. Linares, Miguel Reina-Campos, Shiori Umemura, Mark A. Valasek, Ekihiro Seki, Kanji Yamaguchi, Kazuhiko Koike, Yoshito Itoh, Maria T. Diaz-Meco, Jorge MoscatMichael Karin

研究成果: Article査読

212 被引用数 (Scopus)

抄録

p62 is a ubiquitin-binding autophagy receptor and signaling protein that accumulates in premalignant liver diseases and most hepatocellular carcinomas (HCCs). Although p62 was proposed to participate in the formation of benign adenomas in autophagy-deficient livers, its role in HCC initiation was not explored. Here we show that p62 is necessary and sufficient for HCC induction in mice and that its high expression in non-tumor human liver predicts rapid HCC recurrence after curative ablation. High p62 expression is needed for activation of NRF2 and mTORC1, induction of c-Myc, and protection of HCC-initiating cells from oxidative stress-induced death.

本文言語English
ページ(範囲)935-948
ページ数14
ジャーナルCancer Cell
29
6
DOI
出版ステータスPublished - 2016 6 13
外部発表はい

ASJC Scopus subject areas

  • 腫瘍学
  • 細胞生物学
  • 癌研究

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