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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Nov 23, 2016 |
| Title |
p62, upregulated during preneoplasia, induces hepatocellular carcinogenesis by maintaining survival of stressed HCC-initiating cells |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
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.
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| 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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| Contributor(s) |
Umemura A, He F, Nakagawa H, Yamachika S, Taniguchi K, 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 |
| Citation(s) |
27211490 |
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| Submission date |
Jan 28, 2016 |
| Last update date |
Jul 07, 2022 |
| Contact name |
Jorge Moscat |
| E-mail(s) |
jom4010@med.cornell.edu
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| Organization name |
WEILL CORNELL MEDICINE
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| Department |
Pathology and Laboratory Medicine
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| Lab |
Moscat and Diaz-Meco
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| Street address |
1188 York Avenue
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| City |
New York |
| State/province |
NY |
| ZIP/Postal code |
10065 |
| Country |
USA |
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| Platforms (2) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (12)
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| GSM2049240 |
p62f/f mice AlbCre positive - Specific deletion of p62 in hepatocytes 1 |
| GSM2049241 |
p62f/f mice AlbCre positive - Specific deletion of p62 in hepatocytes 2 |
| GSM2049242 |
p62f/f mice AlbCre positive - Specific deletion of p62 in hepatocytes 3 |
| GSM2049243 |
TSC1f/f Cre positive-1 Specific deletion of TSC1 in hepatocytes |
| GSM2049244 |
TSC1f/f Cre positive-2 Specific deletion of TSC1 in hepatocytes |
| GSM2049245 |
TSC1f/f Cre positive-3 Specific deletion of TSC1 in hepatocytes |
| GSM2049246 |
TSC1f/f / p62f/f mice AlbCre positive - Specific deletion of TSC1 and p62 in hepatocytes 1 |
| GSM2049247 |
TSC1f/f / p62f/f mice AlbCre positive - Specific deletion of TSC1 and p62 in hepatocytes 2 |
| GSM2049248 |
TSC1f/f / p62f/f mice AlbCre positive - Specific deletion of TSC1 and p62 in hepatocytes 3 |
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| Relations |
| BioProject |
PRJNA310105 |
| SRA |
SRP069010 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE77323_DKO_vs_TSC1KONORMAL.deseq.counts.csv.gz |
264.1 Kb |
(ftp)(http) |
CSV |
| GSE77323_p62f_vs_p62fAlbCre.deseq.counts.csv.gz |
261.8 Kb |
(ftp)(http) |
CSV |
SRA Run Selector |
| Processed data are available on Series record |
| Raw data are available in SRA |
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