title: UCH-L1 promotes cancer metastasis in prostate cancer cells through EMT induction.
abstract: 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.
authors.affiliation: Department of Biological Sciences, Inha University, Incheon 402-751, South Korea.
authors.forename: Min Jung
authors.initials: MJ
authors.lastname: Jang
authors.forename: Sung Hee
authors.initials: SH
authors.lastname: Baek
authors.forename: Jung Hwa
authors.initials: JH
authors.lastname: Kim
mesh_terms: D045744:Cell Line, Tumor; D016503:Drug Delivery Systems; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D006801:Humans; D015151:Immunoblotting; D008297:Male; D009362:Neoplasm Metastasis / Q000235:genetics; D009367:Neoplasm Staging; D011401:Promoter Regions, Genetic; D011471:Prostatic Neoplasms / Q000235:genetics / Q000503:physiopathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D043222:Ubiquitin Thiolesterase / Q000235:genetics / Q000378:metabolism*
chemical_list: D043222:Ubiquitin Thiolesterase