title: Ubiquitin C-terminal hydrolase-L3 regulates EMT process and cancer metastasis in prostate cell lines.
abstract: Ubiquitin C-terminal hydrolase-L3 (UCH-L3) is among the deubiquitinating enzymes (DUBs) that cleave ubiquitin (Ub) from Ub precursors or protein substrates. Many DUBs have been shown to participate in cancer progression in various tissues. However, the mechanism and role of UCH-L3 in carcinogenesis has largely been unknown until recently. Here we investigated the implication of UCH-L3 in prostate cancer progression. Interestingly, UCH-L3 is upregulated in normal or non-metastatic prostate cancer cells and is downregulated in metastatic prostate cancer cell lines. Notably, knockdown of UCH-L3 in normal prostate cell line RWPE1 promotes epithelial-to-mesenchymal transition (EMT), an important process for cancer cell invasion and metastasis. The induction of EMT by UCH-L3 knockdown results in an increase of cell migration and invasion. Yet, to the contrary, overexpression of UCH-L3 in highly metastatic prostate cancer cell line PC3 reverses EMT but the active site mutant UCH-L3 did not. Collectively, our findings identify UCH-L3 as a novel EMT regulator in prostate cells and highlight UCH-L3 as a potential therapeutic target for preventing metastatic prostate cancer.
authors.affiliation: Department of Biological Sciences, Inha University, Incheon 402-751, South Korea.
authors.forename: Hyun Min
authors.initials: HM
authors.lastname: Song
authors.affiliation: Department of Biological Sciences, Inha University, Incheon 402-751, South Korea.
authors.forename: Jae Eun
authors.initials: JE
authors.lastname: Lee
authors.affiliation: Department of Biological Sciences, Inha University, Incheon 402-751, South Korea. Electronic address: jhkim4@inha.ac.kr.
authors.forename: Jung Hwa
authors.initials: JH
authors.lastname: Kim
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement; D003546:Cysteine Endopeptidases / Q000235:genetics* / Q000378:metabolism; D015194:Diffusion Chambers, Culture; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D008297:Male; D011467:Prostate / Q000378:metabolism* / Q000473:pathology; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D043222:Ubiquitin Thiolesterase
chemical_list: D034741:RNA, Small Interfering; C509806:UCHL3 protein, human; D043222:Ubiquitin Thiolesterase; D003546:Cysteine Endopeptidases
keywords: EMT; Prostate cancer cells; UCH-L3