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.

journal_name

Genes Dev

journal_title

Genes & development

authors

Hou P,Ma X,Zhang Q,Wu CJ,Liao W,Li J,Wang H,Zhao J,Zhou X,Guan C,Ackroyd J,Jiang S,Zhang J,Spring DJ,Wang YA,DePinho RA

doi

10.1101/gad.326314.119

subject

Has Abstract

pub_date

2019-10-01 00:00:00

pages

1361-1366

issue

19-20

eissn

0890-9369

issn

1549-5477

pii

gad.326314.119

journal_volume

33

pub_type

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