Dai Jin, Qian Chenchen, Su Mingli, Chen Minhu, Chen Jie
Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-Sen University, 58 Zhongshan II road, Guangzhou, Guangdong, 510080, China.
Division of Gastroenterology, Guizhou Provincial People's Hospital, Guiyang, Guizhou, 550002, China.
Tumour Biol. 2016 Sep;37(9):12403-12410. doi: 10.1007/s13277-016-5107-x. Epub 2016 Jun 21.
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.
上皮-间质转化（EMT）在胃癌转移中起重要作用。我们之前的研究表明，胃动素-2（GKN2）可抑制SGC-7901和AGS细胞的转移。在此，我们进一步探讨GKN2在胃癌细胞上皮-间质转化中的作用及其潜在机制。我们发现，GKN2的过表达可降低SGC7901和AGS细胞中Snail的蛋白表达水平，并显著提高E-钙黏蛋白的蛋白水平。进一步的数据表明，敲低Snail可抑制SGC-7901和AGS细胞的迁移和侵袭。已知Snail可被PI3K/AKT通路的下游蛋白GSK3β磷酸化。然后我们检测了PI3K/AKT的下游蛋白p-GSK3β（Ser-9）的蛋白表达，在GKN2过表达的情况下其显著降低。此外，PI3K抑制剂LY294002可逆转siGKN2诱导的E-钙黏蛋白和Snail的蛋白表达变化。综上所述，这些发现表明GKN2通过PI3K/AKT/GSK3β信号通路下调Snail来抑制胃癌细胞的上皮-间质转化。
