Title | p62, Upregulated during Preneoplasia, Induces Hepatocellular Carcinogenesis by Maintaining Survival of Stressed HCC-Initiating Cells. |
Publication Type | Journal Article |
Year of Publication | 2016 |
Authors | Umemura A, He F, Taniguchi K, Nakagawa H, Yamachika S, Font-Burgada J, Zhong Z, Subramaniam S, Raghunandan S, Duran A, Linares JF, Reina-Campos M, Umemura S, Valasek MA, Seki E, Yamaguchi K, Koike K, Itoh Y, Diaz-Meco MT, Moscat J, Karin M |
Journal | Cancer Cell |
Volume | 29 |
Issue | 6 |
Pagination | 935-948 |
Date Published | 2016 06 13 |
ISSN | 1878-3686 |
Keywords | Animals, Carcinoma, Hepatocellular, Cell Survival, Diethylnitrosamine, Gene Expression Regulation, Neoplastic, Humans, Liver Neoplasms, Mechanistic Target of Rapamycin Complex 1, Mice, Mice, Transgenic, Multiprotein Complexes, Neoplasms, Experimental, Neoplastic Stem Cells, NF-E2-Related Factor 2, Proto-Oncogene Proteins c-myc, Sequestosome-1 Protein, TOR Serine-Threonine Kinases, Up-Regulation |
Abstract | 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. |
DOI | 10.1016/j.ccell.2016.04.006 |
Alternate Journal | Cancer Cell |
PubMed ID | 27211490 |
PubMed Central ID | PMC4907799 |
Grant List | R01 DK108743 / DK / NIDDK NIH HHS / United States R01 CA192642 / CA / NCI NIH HHS / United States P01 DK098108 / DK / NIDDK NIH HHS / United States P42 ES010337 / ES / NIEHS NIH HHS / United States R01 CA172025 / CA / NCI NIH HHS / United States R01 CA211794 / CA / NCI NIH HHS / United States P30 CA030199 / CA / NCI NIH HHS / United States P30 CA023100 / CA / NCI NIH HHS / United States R01 CA118165 / CA / NCI NIH HHS / United States R01 CA163798 / CA / NCI NIH HHS / United States R01 CA198103 / CA / NCI NIH HHS / United States |
Related Faculty:
Juan Francisco Linares Rodriguez, Ph.D. Maria Diaz-Meco Conde, Ph.D.