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USP21 deubiquitinase promotes pancreas cancer cell stemness via Wnt pathway activation
The ubiquitin-specific protease (USP) family is the largest group of cysteine proteases. Cancer genomic analysis identified frequent amplification of USP21 (22%) in human pancreatic ductal adenocarcinoma (PDAC). USP21 overexpression correlates with human PDAC progression, and enforced expression of...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory Press
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6771391/ https://www.ncbi.nlm.nih.gov/pubmed/31488580 http://dx.doi.org/10.1101/gad.326314.119 |
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author | Hou, Pingping Ma, Xingdi Zhang, Qiang Wu, Chang-Jiun Liao, Wenting Li, Jun Wang, Huamin Zhao, Jun Zhou, Xin Guan, Carolyn Ackroyd, Jeffery Jiang, Shan Zhang, Jianhua Spring, Denise J. Wang, Y. Alan DePinho, Ronald A. |
author_facet | Hou, Pingping Ma, Xingdi Zhang, Qiang Wu, Chang-Jiun Liao, Wenting Li, Jun Wang, Huamin Zhao, Jun Zhou, Xin Guan, Carolyn Ackroyd, Jeffery Jiang, Shan Zhang, Jianhua Spring, Denise J. Wang, Y. Alan DePinho, Ronald A. |
author_sort | Hou, Pingping |
collection | PubMed |
description | The ubiquitin-specific protease (USP) family is the largest group of cysteine proteases. Cancer genomic analysis identified frequent amplification of USP21 (22%) in human pancreatic ductal adenocarcinoma (PDAC). USP21 overexpression correlates with human PDAC progression, and enforced expression of USP21 accelerates murine PDAC tumor growth and drives PanIN to PDAC progression in immortalized human pancreatic ductal cells. Conversely, depletion of USP21 impairs PDAC tumor growth. Mechanistically, USP21 deubiquitinates and stabilizes the TCF/LEF transcription factor TCF7, which promotes cancer cell stemness. Our work identifies and validates USP21 as a PDAC oncogene, providing a potential druggable target for this intractable disease. |
format | Online Article Text |
id | pubmed-6771391 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Cold Spring Harbor Laboratory Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-67713912020-04-01 USP21 deubiquitinase promotes pancreas cancer cell stemness via Wnt pathway activation Hou, Pingping Ma, Xingdi Zhang, Qiang Wu, Chang-Jiun Liao, Wenting Li, Jun Wang, Huamin Zhao, Jun Zhou, Xin Guan, Carolyn Ackroyd, Jeffery Jiang, Shan Zhang, Jianhua Spring, Denise J. Wang, Y. Alan DePinho, Ronald A. Genes Dev Research Communication The ubiquitin-specific protease (USP) family is the largest group of cysteine proteases. Cancer genomic analysis identified frequent amplification of USP21 (22%) in human pancreatic ductal adenocarcinoma (PDAC). USP21 overexpression correlates with human PDAC progression, and enforced expression of USP21 accelerates murine PDAC tumor growth and drives PanIN to PDAC progression in immortalized human pancreatic ductal cells. Conversely, depletion of USP21 impairs PDAC tumor growth. Mechanistically, USP21 deubiquitinates and stabilizes the TCF/LEF transcription factor TCF7, which promotes cancer cell stemness. Our work identifies and validates USP21 as a PDAC oncogene, providing a potential druggable target for this intractable disease. Cold Spring Harbor Laboratory Press 2019-10-01 /pmc/articles/PMC6771391/ /pubmed/31488580 http://dx.doi.org/10.1101/gad.326314.119 Text en © 2019 Hou et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genesdev.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/. |
spellingShingle | Research Communication Hou, Pingping Ma, Xingdi Zhang, Qiang Wu, Chang-Jiun Liao, Wenting Li, Jun Wang, Huamin Zhao, Jun Zhou, Xin Guan, Carolyn Ackroyd, Jeffery Jiang, Shan Zhang, Jianhua Spring, Denise J. Wang, Y. Alan DePinho, Ronald A. USP21 deubiquitinase promotes pancreas cancer cell stemness via Wnt pathway activation |
title | USP21 deubiquitinase promotes pancreas cancer cell stemness via Wnt pathway activation |
title_full | USP21 deubiquitinase promotes pancreas cancer cell stemness via Wnt pathway activation |
title_fullStr | USP21 deubiquitinase promotes pancreas cancer cell stemness via Wnt pathway activation |
title_full_unstemmed | USP21 deubiquitinase promotes pancreas cancer cell stemness via Wnt pathway activation |
title_short | USP21 deubiquitinase promotes pancreas cancer cell stemness via Wnt pathway activation |
title_sort | usp21 deubiquitinase promotes pancreas cancer cell stemness via wnt pathway activation |
topic | Research Communication |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6771391/ https://www.ncbi.nlm.nih.gov/pubmed/31488580 http://dx.doi.org/10.1101/gad.326314.119 |
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