Usp10, a cytoplasmic ubiquitin-specific protease, belongs to the USP-family DUB with a classic USP domain for deubiquitination. Deubiquitination is a key post-translational protein modification regulating protein homeostasis and various cellular processes [1].

In loss-of-function studies, depletion of Usp10 in hepatocellular carcinoma enhanced polyubiquitination of YAP/TAZ, promoted their proteasomal degradation, and arrested cell proliferation in vitro and in vivo, indicating its role in promoting cancer cell growth through the YAP/TAZ pathway [2]. In lung cancer, loss of Usp10 in mice downregulated KLF4 expression and accelerated KrasG12D-driven lung adenocarcinoma initiation and progression, suggesting its tumor-suppressing role via regulating KLF4 stability [3].

Overall, Usp10 has a dual role in cancers, acting as both an oncogene and a tumor suppressor depending on the cell context. Model-based research, especially KO/CKO mouse models, has revealed its significance in cancer-related biological processes, providing potential therapeutic targets for cancers such as hepatocellular carcinoma, lung cancer, and others [1,2,3].

References:

1. Tao, Li, Liu, Xiao, Jiang, Xinya, Jiang, Shulong, Han, Tao. 2022. USP10 as a Potential Therapeutic Target in Human Cancers. In Genes, 13, . doi:10.3390/genes13050831. https://pubmed.ncbi.nlm.nih.gov/35627217/

2. Zhu, Hong, Yan, Fangjie, Yuan, Tao, He, Qiaojun, Yang, Bo. 2020. USP10 Promotes Proliferation of Hepatocellular Carcinoma by Deubiquitinating and Stabilizing YAP/TAZ. In Cancer research, 80, 2204-2216. doi:10.1158/0008-5472.CAN-19-2388. https://pubmed.ncbi.nlm.nih.gov/32217697/

3. Wang, Xingyun, Xia, Shilin, Li, Hongchang, Zhang, Lingqiang, Han, Chuanchun. 2019. The deubiquitinase USP10 regulates KLF4 stability and suppresses lung tumorigenesis. In Cell death and differentiation, 27, 1747-1764. doi:10.1038/s41418-019-0458-7. https://pubmed.ncbi.nlm.nih.gov/31748695/