Open AccessTIPE 1 suppresses invasion and migration through down‐regulating Wnt/β‐catenin pathway in gastric cancer
Author(s) -
Liu Wenwen,
Chen Ye,
Xie Hua,
Guo Yongmin,
Ren Dandan,
Li Yupeng,
Jing Xu,
Li Dongliang,
Wang Xiao,
Zhao Miaoqing,
Zhu Tianfeng,
Wang Ziying,
Wei Xinbing,
Gao Fei,
Wang Xiaojie,
Liu Suxia,
Zhang Yan,
Yi Fan
Publication year - 2018
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.13362
Subject(s) - metastasis , wnt signaling pathway , cancer , cancer research , gene silencing , epithelial–mesenchymal transition , biology , cancer cell , catenin , signal transduction , microbiology and biotechnology , gene , genetics , biochemistry
Epithelial–mesenchymal transition ( EMT ) plays an important role in the invasiveness and metastasis of gastric cancer. Therefore, identifying key molecules involved in EMT will provide new therapeutic strategy for treating patients with gastric cancer. TIPE 1 is a newly identified member of the TIPE ( TNFAIP 8) family, and its contributions to progression and metastasis have not been evaluated. In this study, we found that the levels of TIPE 1 were significantly reduced and inversely correlated with differentiation status and distant metastasis in primary gastric cancer tissues. We further observed overexpression of TIPE 1 in aggressive gastric cancer cell lines decreased their metastatic properties both in vitro and in vivo as demonstrated by markedly inhibiting EMT and metastasis of gastric cancer cells in nude mice. Consistently, gene silencing of TIPE 1 in well‐differentiated gastric cancer cell line ( AGS ) inhibited these processes. Mechanistically, we found that TIPE 1‐medicated Wnt/β‐catenin signalling was one of the critical signal transduction pathways that link TIPE 1 to EMT inhibition. Importantly, TIPE 1 dramatically restrained the expression and activities of MMP 2 and MMP 9 which are demonstrated to promote tumour progression and are implicated in EMT . Collectively, these findings provide new evidence for a better understanding of the biological activities of TIPE 1 in progression and metastasis of gastric cancer and suggest that TIPE 1 may be an innovative diagnostic and therapeutic target of gastric cancer.