title: Protocadherin 9 inhibits epithelial-mesenchymal transition and cell migration through activating GSK-3β in hepatocellular carcinoma.
abstract: Protocadherin 9 (PCDH9) was found frequently lost in hepatocellular carcinoma (HCC). Here we investigated the role of PCDH9 in the development of HCC. We confirmed that PCDH9 was down-regulated in HCC tissues and cell lines compared with the adjacent non-tumor tissues. PCDH9 downregulation was significantly associated with malignant portal vein invasion of HCC patients. Gain- and loss-of-function studies revealed that downregulation of PCDH9 facilitated tumor cell migration and epithelial-mesenchymal transition (EMT). We identified PCDH9 as a novel regulator of EMT by increasing the activity of GSK-3β and inhibiting Snail1, indicating its potential therapeutic value for reducing metastasis of HCC.
authors.affiliation: Department of Microbiology & Infectious Disease Center, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Zhu
authors.affiliation: Department of Infectious Disease, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Lv
authors.affiliation: Department of Microbiology & Infectious Disease Center, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Ziwei
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Department of Pathology, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Limei
authors.initials: L
authors.lastname: Guo
authors.affiliation: Department of Hepatobiliary Surgery, Henan Cancer Hospital, Zhengzhou, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Microbiology & Infectious Disease Center, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Li
authors.affiliation: Peking University Center for Human Disease Genomics, Department of Immunology, Key Laboratory of Medical Immunology, Ministry of Health, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Wenling
authors.initials: W
authors.lastname: Han
authors.affiliation: Department of Microbiology & Infectious Disease Center, Peking University Health Science Center, Beijing 100191, China. Electronic address: xm_chen6176@bjmu.edu.cn.
authors.forename: Xiangmei
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Microbiology & Infectious Disease Center, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhuang
authors.affiliation: Department of Microbiology & Infectious Disease Center, Peking University Health Science Center, Beijing 100191, China. Electronic address: lu.fengmin@hsc.pku.edu.cn.
authors.forename: Fengmin
authors.initials: F
authors.lastname: Lu
mesh_terms: D015820:Cadherins / Q000235:genetics* / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics* / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011169:Portal Vein / Q000378:metabolism / Q000473:pathology; D000091363:Protocadherins; D015398:Signal Transduction; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D015820:Cadherins; C115817:PCDH9 protein, human; D000091363:Protocadherins; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3
keywords: EMT; GSK-3β; Hepatocellular carcinoma; Protocadherin 9; Tumor suppressor gene