title: FAT1 prevents epithelial mesenchymal transition (EMT) via MAPK/ERK signaling pathway in esophageal squamous cell cancer.
abstract: FAT1 regulates cell-cell adhesion, cell growth, cell migration, and actin dynamics as either oncogene or tumor suppressor in human cancers. We previously identified FAT1 was one of significant mutant genes in esophageal squamous cell carcinoma (ESCC). However, the function and underlying mechanism of FAT1 in ESCC have not been explored. In this study, we report that FAT1 expression was significantly lower in ESCC tumor tissues. Exogenous expression of FAT1 led to inhibition of cell proliferation and colony formation, as well as cell migration and invasion whereas FAT1 knockdown showed the opponent trends in vitro and in vivo. Moreover, FAT1 knockdown led to a statistically decrease of E-cadherin expression and a dramatically increase expression of N-cadherin, Vimentin, and Snail in a MAPK/ERK pathway-dependent manner. Meanwhile, over-expression of FAT1 resulted in the opposite trends. These alterations were abrogated in the presence of U0126, a MEK specific inhibitor. Collectively, our studies identified a novel role for FAT1 in inhibiting tumor growth and EMT occurrence in ESCC. We proposed that disruption of MAPK/ERK pathway by FAT1 contributes the EMT in ESCC and has important implications for understanding ESCC development.
authors.affiliation: Translational Medicine Research Center, Shanxi Medical University, Taiyuan, Shanxi 030001, PR China; Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan, Shanxi 030001, PR China; Department of Pharmacology, Shanxi Medical University, Taiyuan, Shanxi 030001, PR China.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Hu
authors.affiliation: Translational Medicine Research Center, Shanxi Medical University, Taiyuan, Shanxi 030001, PR China; Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan, Shanxi 030001, PR China; Department of Anatomy, Shanxi Medical University, Taiyuan, Shanxi 030001, PR China.
authors.forename: Yuanfang
authors.initials: Y
authors.lastname: Zhai
authors.affiliation: Translational Medicine Research Center, Shanxi Medical University, Taiyuan, Shanxi 030001, PR China; Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan, Shanxi 030001, PR China.
authors.forename: Pengzhou
authors.initials: P
authors.lastname: Kong
authors.affiliation: Translational Medicine Research Center, Shanxi Medical University, Taiyuan, Shanxi 030001, PR China; Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan, Shanxi 030001, PR China.
authors.forename: Heyang
authors.initials: H
authors.lastname: Cui
authors.affiliation: Translational Medicine Research Center, Shanxi Medical University, Taiyuan, Shanxi 030001, PR China; Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan, Shanxi 030001, PR China.
authors.forename: Ting
authors.initials: T
authors.lastname: Yan
authors.affiliation: Translational Medicine Research Center, Shanxi Medical University, Taiyuan, Shanxi 030001, PR China; Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan, Shanxi 030001, PR China.
authors.forename: Jian
authors.initials: J
authors.lastname: Yang
authors.affiliation: Translational Medicine Research Center, Shanxi Medical University, Taiyuan, Shanxi 030001, PR China; Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan, Shanxi 030001, PR China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Qian
authors.affiliation: Translational Medicine Research Center, Shanxi Medical University, Taiyuan, Shanxi 030001, PR China; Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan, Shanxi 030001, PR China.
authors.forename: Yanchun
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Translational Medicine Research Center, Shanxi Medical University, Taiyuan, Shanxi 030001, PR China; Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan, Shanxi 030001, PR China.
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.affiliation: Translational Medicine Research Center, Shanxi Medical University, Taiyuan, Shanxi 030001, PR China; Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan, Shanxi 030001, PR China.
authors.forename: Hongyi
authors.initials: H
authors.lastname: Li
authors.affiliation: Translational Medicine Research Center, Shanxi Medical University, Taiyuan, Shanxi 030001, PR China; Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan, Shanxi 030001, PR China; Department of Pathology, The First Hospital, Shanxi Medical University, Taiyuan, Shanxi 030001, PR China.
authors.forename: Caixia
authors.initials: C
authors.lastname: Cheng
authors.affiliation: Translational Medicine Research Center, Shanxi Medical University, Taiyuan, Shanxi 030001, PR China; Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan, Shanxi 030001, PR China.
authors.forename: Ling
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Translational Medicine Research Center, Shanxi Medical University, Taiyuan, Shanxi 030001, PR China; Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan, Shanxi 030001, PR China.
authors.forename: Zhiwu
authors.initials: Z
authors.lastname: Jia
authors.affiliation: Translational Medicine Research Center, Shanxi Medical University, Taiyuan, Shanxi 030001, PR China; Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan, Shanxi 030001, PR China; Department of Anorectum, Shanxi Provincial People's Hospital, Taiyuan, Shanxi 030001, PR China.
authors.forename: Yaoping
authors.initials: Y
authors.lastname: Li
authors.affiliation: Translational Medicine Research Center, Shanxi Medical University, Taiyuan, Shanxi 030001, PR China; Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan, Shanxi 030001, PR China; Department of General Surgery, Shanxi Cancer Hospital, Taiyuan, Shanxi 030001, PR China.
authors.forename: Bin
authors.initials: B
authors.lastname: Yang
authors.affiliation: Translational Medicine Research Center, Shanxi Medical University, Taiyuan, Shanxi 030001, PR China; Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan, Shanxi 030001, PR China; Department of Pathology, Shanxi Cancer Hospital, Taiyuan, Shanxi 030001, PR China.
authors.forename: Enwei
authors.initials: E
authors.lastname: Xu
authors.affiliation: Translational Medicine Research Center, Shanxi Medical University, Taiyuan, Shanxi 030001, PR China; Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan, Shanxi 030001, PR China.
authors.forename: Juan
authors.initials: J
authors.lastname: Wang
authors.affiliation: Translational Medicine Research Center, Shanxi Medical University, Taiyuan, Shanxi 030001, PR China; Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan, Shanxi 030001, PR China.
authors.forename: Jie
authors.initials: J
authors.lastname: Yang
authors.affiliation: Translational Medicine Research Center, Shanxi Medical University, Taiyuan, Shanxi 030001, PR China; Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan, Shanxi 030001, PR China.
authors.forename: Yanghui
authors.initials: Y
authors.lastname: Bi
authors.affiliation: Translational Medicine Research Center, Shanxi Medical University, Taiyuan, Shanxi 030001, PR China; Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan, Shanxi 030001, PR China.
authors.forename: Lu
authors.initials: L
authors.lastname: Chang
authors.affiliation: Translational Medicine Research Center, Shanxi Medical University, Taiyuan, Shanxi 030001, PR China; Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan, Shanxi 030001, PR China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Translational Medicine Research Center, Shanxi Medical University, Taiyuan, Shanxi 030001, PR China; Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan, Shanxi 030001, PR China; Department of Anatomy, Shanxi Medical University, Taiyuan, Shanxi 030001, PR China.
authors.forename: Yingchun
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Translational Medicine Research Center, Shanxi Medical University, Taiyuan, Shanxi 030001, PR China; Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan, Shanxi 030001, PR China; Department of Oncology, The First Hospital, Shanxi Medical University, Taiyuan, Shanxi 030001, PR China.
authors.forename: Bin
authors.initials: B
authors.lastname: Song
authors.affiliation: Department of Otorhinolaryngology, Shanxi Provincial People's Hospital, Taiyuan, Shanxi 030001, PR China.
authors.forename: Guodong
authors.initials: G
authors.lastname: Li
authors.affiliation: Translational Medicine Research Center, Shanxi Medical University, Taiyuan, Shanxi 030001, PR China; Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan, Shanxi 030001, PR China.
authors.forename: Ruyi
authors.initials: R
authors.lastname: Shi
authors.affiliation: Translational Medicine Research Center, Shanxi Medical University, Taiyuan, Shanxi 030001, PR China; Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan, Shanxi 030001, PR China; Department of General Surgery, The First Hospital, Shanxi Medical University, Taiyuan, Shanxi 030001, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Pharmacology, Shanxi Medical University, Taiyuan, Shanxi 030001, PR China.
authors.forename: Mingsheng
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Translational Medicine Research Center, Shanxi Medical University, Taiyuan, Shanxi 030001, PR China; Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan, Shanxi 030001, PR China; Department of Anatomy, Shanxi Medical University, Taiyuan, Shanxi 030001, PR China.
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Cheng
authors.affiliation: Translational Medicine Research Center, Shanxi Medical University, Taiyuan, Shanxi 030001, PR China; Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan, Shanxi 030001, PR China. Electronic address: cuiyp@sxmu.edu.cn.
authors.forename: Yongping
authors.initials: Y
authors.lastname: Cui
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D004938:Esophageal Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D000077277:Esophageal Squamous Cell Carcinoma; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D009154:Mutation; D009361:Neoplasm Invasiveness; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D034622:RNA Interference; D000071250:Snail Family Transcription Factors / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014162:Transfection; D047368:Tumor Burden; D014746:Vimentin / Q000235:genetics / Q000378:metabolism
chemical_list: D015703:Antigens, CD; C513384:CDH1 protein, human; C050361:CDH2 protein, human; D015820:Cadherins; C502403:FAT1 protein, human; D047428:Protein Kinase Inhibitors; D000071250:Snail Family Transcription Factors; D014746:Vimentin; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: EMT; ESCC; FAT1; MAPK pathway; Tumor suppressor