Differential Regulation of Cancer Metastasis by UCH-L1 and UCH-L3 in Prostate Cells

초록

Ubiquitin C-terminal hydrolyase-L1 (UCH-L1) and UCH-L3 are closely related deubiquitinating enzyme family members with about 53% amino acid sequence identity. However, they show distinct tissue distribution and have differential biochemical traits. Here we investigated the differential functions of these two isozymes in the progression of prostate cancer. We found that UCH-L1 is specifically highly expressed in metastatic prostate cancer cell line DU145, but not in normal or weakly metastatic prostate cancer cells. In contrast, UCH-L3 expression is high in normal prostate cells and low in metastatic prostate cancer cells. To figure out the role of UCH-L1 and UCH-L3 in prostate cancer metastasis, we constructed the stable cell lines converting each protein level by knockdown or overexpression. Notably, expression of UCH-L1 in RWPE1 promotes epithelial-to-mesenchymal transition (EMT), an important process for cancer cell invasion and metastasis. On the contrary, knockdown of UCH-L3 in RWPE1 promotes EMT. These results demonstrate that closely related UCH-L1 and UCH-L3 function differentially to regulate the prostate cancer metastasis.