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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...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2019
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.
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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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