title: SENP1 regulates hepatocyte growth factor-induced migration and epithelial-mesenchymal transition of hepatocellular carcinoma.
abstract: The deregulation of HGF/c-Met signaling is implicated in epithelial-mesenchymal transition (EMT) and progress of hepatocellular carcinoma (HCC). However, the epigenetic mechanisms that HGF/c-Met regulates EMT and metastasis of HCC cells are less explored. In this study, we demonstrated that HCC cells express a high level of SUMO/sentrin-specific protease 1 (Senp1) which is induced by HGF/c-Met signals. Lentivirus-mediated small hairpin RNA (shRNA) transduction results in Senp1 silence in HCC cells. Senp1 silence reduces the HGF-induced proliferation and migration of HCC cells. Senp1 inhibition also induces HCC cell apoptosis and growth arrest. Furthermore, Senp1 knockdown inhibits epithelial-to-mesenchymal transition, with increase of E-cadherin and ZO-1 expression, decrease of fibronectin and N-cadherin expression. The EMT-related transcription factor Zeb1 was SUMO-modified and decreased in Senp1-silenced HCC cells. These results delineate that senp1 might play an important role in the regulation of HGF-induced invasion and migration of HCC cells.
authors.affiliation: Department of Gastroenterology, Shenyang General Hospital of PLA, 83 Wenhua Road, Shenyang, 110016, People's Republic of China.
authors.forename: Wenwen
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing, 100850, People's Republic of China.
authors.forename: Huiyan
authors.initials: H
authors.lastname: Sun
authors.affiliation: Qinghai Provincial People's Hospital, Xining, 810007, People's Republic of China.
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Shi
authors.affiliation: Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing, 100850, People's Republic of China.
authors.forename: Hua
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing, 100850, People's Republic of China.
authors.forename: Chunping
authors.initials: C
authors.lastname: Cui
authors.affiliation: Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing, 100850, People's Republic of China.
authors.forename: Fengjun
authors.initials: F
authors.lastname: Xiao
authors.affiliation: Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing, 100850, People's Republic of China.|Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors.forename: ChuTse
authors.initials: C
authors.lastname: Wu
authors.affiliation: Department of Gastroenterology, Shenyang General Hospital of PLA, 83 Wenhua Road, Shenyang, 110016, People's Republic of China. guoxiaozhong1962@163.com.
authors.forename: Xiaozhong
authors.initials: X
authors.lastname: Guo
authors.affiliation: Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing, 100850, People's Republic of China. wangls@bmi.ac.cn.|Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China. wangls@bmi.ac.cn.
authors.forename: Lisheng
authors.initials: L
authors.lastname: Wang
mesh_terms: D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000473:pathology*; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000235:genetics; D059447:Cell Cycle Checkpoints; D002455:Cell Division; D045744:Cell Line, Tumor; D002465:Cell Movement; D003546:Cysteine Endopeptidases; D010450:Endopeptidases / Q000235:genetics / Q000502:physiology*; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D017228:Hepatocyte Growth Factor / Q000502:physiology; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000473:pathology*; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D011499:Protein Processing, Post-Translational; D019859:Proto-Oncogene Proteins c-met / Q000502:physiology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D058207:Sumoylation; D000071799:Zinc Finger E-box-Binding Homeobox 1 / Q000378:metabolism
chemical_list: D015815:Cell Adhesion Molecules; C066855:HGF protein, human; D009363:Neoplasm Proteins; D034741:RNA, Small Interfering; C486307:ZEB1 protein, human; D000071799:Zinc Finger E-box-Binding Homeobox 1; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met; D010450:Endopeptidases; C404512:SENP1 protein, human; D003546:Cysteine Endopeptidases
keywords: EMT; HCC; Senp1; Zeb1