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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 druggable target for this intractable disease.

SUBMITTER: Hou P

PROVIDER: S-EPMC6771391 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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USP21 deubiquitinase promotes pancreas cancer cell stemness via Wnt pathway activation.

Hou Pingping P Ma Xingdi X Zhang Qiang Q Wu Chang-Jiun CJ Liao Wenting W Li Jun J Wang Huamin H Zhao Jun J Zhou Xin X Guan Carolyn C Ackroyd Jeffery J Jiang Shan S Zhang Jianhua J Spring Denise J DJ Wang Y Alan YA DePinho Ronald A RA

Genes & development 20190905 19-20

The ubiquitin-specific protease (USP) family is the largest group of cysteine proteases. Cancer genomic analysis identified frequent amplification of <i>USP21</i> (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. Mechanis ...[more]

PMID: 31488580

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USP21 deubiquitinase promotes pancreas cancer cell stemness via Wnt pathway activation.

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USP21 deubiquitinase promotes pancreas cancer cell stemness via Wnt pathway activation.

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