USP21 deubiquitinase promotes pancreas cancer cell stemness via Wnt pathway activation
Menée in vitro et à l'aide d'un modèle murin d'adénocarcinome canalaire du pancréas, cette étude met en évidence un mécanisme par lequel la déubiquitinase USP21 favorise la croissance des cellules souches cancéreuses en activant la voie de signalisation des glycoprotéines Wnt
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.