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.
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 druggable target for this intractable disease.
Funder
Hirshberg Foundation for Pancreatic Cancer Research
Cancer Center
National Cancer Institute
Publisher
Cold Spring Harbor Laboratory
Subject
Developmental Biology,Genetics
Cited by
71 articles.
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