Epithelial-mesenchymal transition (EMT) plays an important role in metastasis of gastric cancer. Our previous study showed that Gastrokine-2 (GKN2) can inhibit the metastasis of SGC-7901 and AGS cells. Herein, we further explored the role of GKN2 in epithelial mesenchymal transition of gastric cancer cells and the underlying mechanisms. We found that overexpression of GKN2 can lower the protein expression level of Snail and markedly elevate E-cadherin protein level in SGC7901 and AGS cells. Further data showed that knockdown of snail can inhibit the migration and invasion of SGC-7901 and AGS cells. It is known that Snail can be phosphorylated by GSK3β, a downstream protein of PI3K/AKT pathway. We then test protein expression of p-GSK3β(Ser-9), the downstream protein of PI3K/AKT, which was significantly decreased under the circumstance of GKN2 overexpression. Moreover, LY294002, a PI3K inhibitor, can reverse the protein expression change of E-cadherin and snail induced by siGKN2. Taken together, these findings suggested that GKN2 suppressed epithelial mesenchymal transition of gastric cancer cells by downregulation of snail through PI3K/AKT/GSK3β signaling pathway.
Gastrokine-2 Gastric cancer Metastasis Epithelial mesenchymal transition
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This study was supported by grants from the National Natural Science Foundation of China (No. 30871145 and 81072048).
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