UCH-L1 promotes cancer metastasis in prostate cancer cells through EMT induction

Ubiquitin C-terminal hydrolse-L1 (UCH-L1) is a deubiquitinating enzyme (DUB) that cleaves the ubiquitin (ub) moiety from ub precursors or protein substrates. The correlation between UCH-L1 and cancer has been reported in various tissues, but the role of UCH-L1 in prostate cancer has not been thoroughly researched. Here we found that UCH-L1 is specifically highly expressed in the metastatic DU145 prostate cancer cell line, but not in the benign or weakly metastatic prostate cancer cells. To determine the role of UCH-L1 in prostate cancer metastasis, we constructed UCH-L1-knockdown DU145 and UCH-L1 or the active site mutant form of UCH-L1 (UCH-L1 C90S) expressing RWPE1 stable cells. Notably, the expression of UCH-L1 in RWPE1 cells promotes epithelial-to-mesenchymal transition (EMT), and this is an important process for cancer cell invasion and metastasis. On the contrary, knockdown of UCH-L1 in DU145 cells induces MET, the reverse program of EMT. Furthermore, the change of EMT status caused by altering the UCH-L1 level affects the migration and invasiveness of prostate cancer cells. Our results indicate that UCH-L1 promotes prostate cancer metastasis through EMT induction and UCH-L1 could be a novel diagnostic and therapeutic target for prostate cancer treatment.