Gastrokine 1 functions as a tumor suppressor by inhibition of epithelial-mesenchymal transition in gastric cancers

被引:45
作者
Yoon, Jung Hwan [1 ]
Kang, Young Hwi [1 ]
Choi, Yoo Jin [1 ]
Park, In Soo [2 ]
Nam, Suk Woo [1 ]
Lee, Jung Young [1 ]
Lee, Yun Sil [3 ,4 ]
Park, Won Sang [1 ]
机构
[1] Catholic Univ Korea, Dept Pathol, Coll Med, Seoul 137701, South Korea
[2] Catholic Univ Korea, Dept Gen Surg, Coll Med, Seoul 137701, South Korea
[3] Ewha Womans Univ, Coll Pharm, Seoul 120750, South Korea
[4] Ewha Womans Univ, Div Life Sci & Pharmaceut, Seoul 120750, South Korea
基金
新加坡国家研究基金会;
关键词
GKN1; Tumor suppressor; Gastric cancer; Progression; EMT; CARCINOMA; PROTEIN; CELLS; EXPRESSION; AMP-18;
D O I
10.1007/s00432-011-1051-8
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Gastrokine 1 (GKN1) plays an important role in the gastric mucosal defense mechanism and also acts as a functional gastric tumor suppressor. The specific aim of this study was to determine the molecular mechanisms underlying GKN1 tumor suppressor activity in the progression of gastric cancers. We examined the effect of GKN1 on epithelial-mesenchymal transition (EMT) and cell migration in GKN1-transfected and recombinant GKN1-treated AGS gastric cancer cells using in vitro wound healing, microchemotaxis, and invasion assays. In GKN1-transfected AGS cells, we observed inhibition of cell migration and invasion in wound healing, transwell and Matrigel assay. Also, GKN1-transfected and recombinant GKN1-treated AGS cells showed decreased levels of ROS and expression of phosphatidylinositol 3-kinase (PI3K)/Akt pathway proteins, concomitant with re-expression of E-cadherin and decreased expression of cytoplasmic and nuclear expression of beta-catenin, slug, snail, fibronectin, and vimentin. These data suggest that the GKN1 gene may play an important role in the progression of sporadic gastric cancers via inhibition of EMT and cancer cell migration.
引用
收藏
页码:1697 / 1704
页数:8
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