Abstract
PURPOSE: 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. METHODS: 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. RESULTS: 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 β-catenin, slug, snail, fibronectin, and vimentin. CONCLUSIONS: 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.