USP21 deubiquitinase promotes pancreas cancer cell stemness via Wnt pathway activation

Pingping Hou; Xingdi Ma; Qiang Zhang; Chang Jiun Wu; Wenting Liao; Jun Li; Huamin Wang; Jun Zhao; Xin Zhou; Carolyn Guan; Jeffery Ackroyd; Shan Jiang; Jianhua Zhang; Denise J. Spring; Y. Alan Wang; Ronald A. DePinho

doi:10.1101/gad.326314.119

USP21 deubiquitinase promotes pancreas cancer cell stemness via Wnt pathway activation

Pingping Hou, Xingdi Ma, Qiang Zhang, Chang Jiun Wu, Wenting Liao, Jun Li, Huamin Wang, Jun Zhao, Xin Zhou, Carolyn Guan, Jeffery Ackroyd, Shan Jiang, Jianhua Zhang, Denise J. Spring, Y. Alan Wang, Ronald A. DePinho

Research output: Contribution to journal › Article › peer-review

63 Scopus citations

Abstract

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 drug-gable target for this intractable disease.

Original language	English (US)
Pages (from-to)	1361-1366
Number of pages	6
Journal	Genes and Development
Volume	33
Issue number	19-20
DOIs	https://doi.org/10.1101/gad.326314.119
State	Published - Oct 1 2019

Keywords

Cancer stemness
Deubiquitinase
Pancreatic cancer
TCF7
USP21
Wnt pathway

ASJC Scopus subject areas

Genetics
Developmental Biology

MD Anderson CCSG core facilities

Advanced Technology Genomics Core
Bioinformatics Shared Resource
Research Animal Support Facility
Tissue Biospecimen and Pathology Resource

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10.1101/gad.326314.119

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title = "USP21 deubiquitinase promotes pancreas cancer cell stemness via Wnt pathway activation",

abstract = "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 drug-gable target for this intractable disease.",

keywords = "Cancer stemness, Deubiquitinase, Pancreatic cancer, TCF7, USP21, Wnt pathway",

author = "Pingping Hou and Xingdi Ma and Qiang Zhang and Wu, {Chang Jiun} and Wenting Liao and Jun Li and Huamin Wang and Jun Zhao and Xin Zhou and Carolyn Guan and Jeffery Ackroyd and Shan Jiang and Jianhua Zhang and Spring, {Denise J.} and {Alan Wang}, Y. and DePinho, {Ronald A.}",

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AU - Hou, Pingping

AU - Ma, Xingdi

AU - Zhang, Qiang

AU - Wu, Chang Jiun

AU - Liao, Wenting

AU - Li, Jun

AU - Wang, Huamin

AU - Zhao, Jun

AU - Zhou, Xin

AU - Guan, Carolyn

AU - Ackroyd, Jeffery

AU - Jiang, Shan

AU - Zhang, Jianhua

AU - Spring, Denise J.

AU - Alan Wang, Y.

AU - DePinho, Ronald A.

N1 - Publisher Copyright: © 2019 Hou et al. 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/.

PY - 2019/10/1

Y1 - 2019/10/1

N2 - 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 drug-gable target for this intractable disease.

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USP21 deubiquitinase promotes pancreas cancer cell stemness via Wnt pathway activation

Abstract

Keywords

ASJC Scopus subject areas

MD Anderson CCSG core facilities

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