Usp32-flox Mouse

Usp32, or ubiquitin-specific peptidase 32, is a crucial member of the ubiquitin-specific protease family. It functions as a deubiquitinating enzyme, specifically hydrolyzing ubiquitin molecules from ubiquitin-linked proteins, thereby inversely regulating protein degradation and affecting protein function. It is associated with the ubiquitin-proteasome pathway, an essential protein regulatory system in cells [1].

Knockout (KO) of USP32 in primary hTERT-RPE1 cells leads to hyperubiquitination of LAMTOR1, impairing mTORC1 recruitment, decreasing mTORC1 activity, and inducing autophagy, revealing its role in the regulation of the mTORC1 activation cascade at lysosomes [2]. In gastric cancer (GC), knockdown or depletion of USP32 significantly inhibits GC cell proliferation and migration in vitro and in vivo, indicating its oncogenic function [3]. In non-small cell lung cancer (NSCLC), interference with USP32 inhibits cell proliferation, migration, and EMT development [4]. In hepatocellular carcinoma (HCC), knockdown of USP32 represses cell proliferation, colony formation, and migration in vitro and inhibits tumor growth in vivo [5]. In gastrointestinal stromal tumours (GISTs), loss of Rab35, which is regulated by USP32, decreases exosome secretion and hampers the transmission of imatinib resistance [6]. In breast cancers, USP32 confers resistance to YM155 by promoting ER-associated degradation of SLC35F2 [7]. In colorectal carcinoma (CRC), USP32 is critical for cell proliferation, survival, and migration, and tumour growth, likely due to activation of the NF-κB signalling pathway [8]. In gastric cancer, USP32 silencing blocks the expression of SHMT2 and reverts cancer development [9].

In conclusion, Usp32 plays a significant role in multiple biological processes and disease conditions, especially in various cancers. Gene knockout models, such as the KO of USP32 in different cell lines and animal models, have been instrumental in revealing its functions in cancer cell proliferation, migration, drug resistance, and the regulation of key signalling pathways. These findings suggest that Usp32 could be a potential therapeutic target for cancer treatment.