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.

中文翻译：

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USP21去泛素酶通过Wnt途径激活促进胰腺癌细胞的干性。

泛素特异性蛋白酶（USP）家族是最大的半胱氨酸蛋白酶。癌症基因组分析确定了USP21在人胰管腺癌（PDAC）中的频繁扩增（22％）。USP21的过表达与人类PDAC的进展相关，并且USP21的强制表达加速了小鼠PDAC肿瘤的生长，并在永生化的人胰管细胞中驱动PanIN进入PDAC的进展。相反，USP21的消耗会损害PDAC肿瘤的生长。从机理上讲，USP21使泛素化并稳定TCF / LEF转录因子TCF7，从而促进癌细胞的干性。我们的工作确定并确认USP21是PDAC致癌基因，为这种顽固性疾病提供了潜在的可药物治疗靶标。