title: FAT4 functions as a tumour suppressor in gastric cancer by modulating Wnt/β-catenin signalling.
abstract: BACKGROUND
  FAT4, a cadherin-related protein, was shown to function as a tumour suppressor; however, its role in human gastric cancer remains largely unknown. Here, we investigated the role of FAT4 in gastric cancer and examined the underlying molecular mechanisms.
  
  
  METHODS
  The expression of FAT4 was evaluated by immunohistochemistry, western blotting, and qRT-PCR in relation to the clinicopathological characteristics of gastric cancer patients. The effects of FAT4 silencing on cell proliferation, migration, and invasion were assessed by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium) assay, and migration and invasion assays in gastric cancer cell lines in vitro and in a mouse xenograft model in vivo.
  
  
  RESULTS
  Downregulation of FAT4 expression in gastric cancer tissues compared with adjacent normal tissues was correlated with lymph-node metastasis and poor survival. Knockdown of FAT4 promoted the growth and invasion of gastric cancer cells via the activation of Wnt/β-catenin signalling, and induced epithelial-to-mesenchymal transition (EMT) in gastric cancer cells, as demonstrated by the upregulation and downregulation of mesenchymal and epithelial markers. Silencing of FAT4 promoted tumour growth and metastasis in a gastric cancer xenograft model in vivo.
  
  
  CONCLUSIONS
  FAT4 has a tumour suppressor role mediated by the modulation of Wnt/β-catenin signalling, providing potential novel targets for the treatment of gastric cancer.
authors.affiliation: Department of General Surgery, Institute of Anal-Colorectal Surgery, No. 150 Central Hospital of PLA, No. 2, Huaxiaxi Road, Luoyang 471031, China.|Department of General Surgery, The No. 150 Clinical Medical College, Second Military Medical University, Shanghai 200433, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Cai
authors.affiliation: Department of Oncology, Shanghai Changhai Hospital, 168 Changhai Road, Shanghai 200433, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Feng
authors.affiliation: Department of General Surgery, Institute of Anal-Colorectal Surgery, No. 150 Central Hospital of PLA, No. 2, Huaxiaxi Road, Luoyang 471031, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Hu
authors.affiliation: Department of General Surgery, Institute of Anal-Colorectal Surgery, No. 150 Central Hospital of PLA, No. 2, Huaxiaxi Road, Luoyang 471031, China.
authors.forename: Haiyang
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of General Surgery, Institute of Anal-Colorectal Surgery, No. 150 Central Hospital of PLA, No. 2, Huaxiaxi Road, Luoyang 471031, China.
authors.forename: Guangzhen
authors.initials: G
authors.lastname: Yang
authors.affiliation: Department of Gastrointestinal Surgery, Shanghai Changzheng Hospital, 415 Fengyang Road, Shanghai 200003, China.
authors.forename: Qingping
authors.initials: Q
authors.lastname: Cai
authors.affiliation: Department of General Surgery, Institute of Anal-Colorectal Surgery, No. 150 Central Hospital of PLA, No. 2, Huaxiaxi Road, Luoyang 471031, China.|Department of General Surgery, The No. 150 Clinical Medical College, Second Military Medical University, Shanghai 200433, China.
authors.forename: Chunfang
authors.initials: C
authors.lastname: Gao
authors.affiliation: Department of General Surgery, Institute of Anal-Colorectal Surgery, No. 150 Central Hospital of PLA, No. 2, Huaxiaxi Road, Luoyang 471031, China.|Department of General Surgery, The No. 150 Clinical Medical College, Second Military Medical University, Shanghai 200433, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Wei
mesh_terms: D000818:Animals; D015820:Cadherins / Q000235:genetics / Q000502:physiology*; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D055785:Gene Knockdown Techniques; D016147:Genes, Tumor Suppressor; D064593:Heterografts; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000502:physiology*; D051153:Wnt Proteins / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D015820:Cadherins; C534294:FAT4 protein, human; D025521:Tumor Suppressor Proteins; D051153:Wnt Proteins; D051176:beta Catenin