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Title: p62, upregulated during preneoplasia, induces hepatocellular carcinogenesis by maintaining survival of stressed HCC-initiating cells      
keywords:
Transcriptome or Gene expression
ID:
PRJNA310105
description:
p62/SQSTM1 is a ubiquitin-binding autophagy receptor and signaling protein that accumulates in premalignant liver diseases and most hepatocellular carcinomas (HCC). Although p62 was proposed to participate in 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 level in non-tumor human liver predicts rapid HCC recurrence after curative ablation. High p62 expression is needed for activation of NRF2 and mTORC1, c-Myc induction and protection of HCC-initiating cells from oxidative stress-induced death. Overall design: p62F/F and Tsc1 F/F mice (Mori et al., 2009; Muller et al., 2013) were backcrossed to C57BL/6 mice for at least 7 generations, and then bred with Alb-Cre transgenic mice (also on C57BL/6 background) to generate p62F/F; Alb-Cre (p62Δhep) and Tsc1F/F; Alb-Cre (Tsc1Δhep)mice, respectively. p62Δhep mice were crossed to Tsc1Δhep and MUP-uPA mice to generate p62F/F; Tsc1F/F; Alb-Cre (Tsc1/p62Δhep) mice and p62Δhep/MUP-uPA transgenic mice, respectively. Genotyping was performed as described (Muller et al., 2013). All animal studies were in accordance with NIH guidelines for use and care of live animals and were approved by the UCSD Institutional Animal Care and Use Committee. Mice were maintained in filter-topped cages on autoclaved chow diet (low-fat diet; LFD, composed of 12% fat, 23% protein, 65% carbohydrates based on caloric content) or high-fat diet (HFD, composed of 59% fat, 15% protein, 26% carbohydrates based on caloric content; Bio-Serv) and water at UCSD according to NIH Guidelines.
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landingpage: http://www.ncbi.nlm.nih.gov/bioproject/PRJNA310105
authentication:
none
authorization:
none
ID:
pmid:27211490
name:
Mus musculus
ncbiID:
ncbitax:10090
abbreviation:
NCBI
homePage: http://www.ncbi.nlm.nih.gov
ID:
SCR:006472
name:
National Center for Biotechnology Information
homePage: http://www.ncbi.nlm.nih.gov/bioproject
ID:
SCR:004801
name:
NCBI BioProject