FAT4 functions as a tumour suppressor in gastric cancer by modulating Wnt/β-catenin signalling

被引：60
作者：
Cai, Jian [1 ,2 ]
Feng, Dan [3 ]
Hu, Liang [1 ]
Chen, Haiyang [1 ]
Yang, Guangzhen [1 ]
Cai, Qingping [4 ]
Gao, Chunfang [1 ,2 ]
Wei, Dong [1 ,2 ]
机构：
[1] PLA, Cent Hosp 150, Inst Anal Colorectal Surg, Dept Gen Surg, Luoyang 471031, Peoples R China
[2] Second Mil Med Univ, Dept Gen Surg, Clin Med Coll 150, Shanghai 200433, Peoples R China
[3] Shanghai Changhai Hosp, Dept Oncol, Shanghai 200433, Peoples R China
[4] Shanghai Changzheng Hosp, Dept Gastrointestinal Surg, Shanghai 200003, Peoples R China
来源：
BRITISH JOURNAL OF CANCER | 2015年 / 113卷 / 12期
关键词：
FAT4; gastric cancer; metastasis; Wnt/beta-catenin; EMT; BETA-CATENIN; MATRIX-METALLOPROTEINASE; PROTOCADHERIN FAT1; HIPPO PATHWAY; ACTIVATION; CADHERINS; GENE; IDENTIFICATION; PROGRESSION; EXPRESSION;
D O I：
10.1038/bjc.2015.367
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
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/beta-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/b-catenin signalling, providing potential novel targets for the treatment of gastric cancer.
引用
收藏
页码：1720 / 1729
页数：10
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