Gastrokine-2 suppresses epithelial mesenchymal transition through PI3K/AKT/GSK3β signaling in gastric cancer.
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.
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.
Jin
J
Dai
Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-Sen University, 58 Zhongshan II road, Guangzhou, Guangdong, 510080, China.
Chenchen
C
Qian
Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-Sen University, 58 Zhongshan II road, Guangzhou, Guangdong, 510080, China.
Mingli
M
Su
Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-Sen University, 58 Zhongshan II road, Guangzhou, Guangdong, 510080, China. chenminhu@vip.163.com.
Minhu
M
Chen
Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-Sen University, 58 Zhongshan II road, Guangzhou, Guangdong, 510080, China. chen0jie@hotmail.com.
Jie
J
Chen
D015703:Antigens, CD; D015820:Cadherins / Q000502:physiology; D002352:Carrier Proteins / Q000502:physiology*; D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition; D000071679:Glycogen Synthase Kinase 3 beta / Q000502:physiology*; D006801:Humans; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D000071250:Snail Family Transcription Factors / Q000502:physiology; D013274:Stomach Neoplasms / Q000473:pathology*
D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins; D002352:Carrier Proteins; C503073:GKN2 protein, human; D000071250:Snail Family Transcription Factors; D019869:Phosphatidylinositol 3-Kinases; D000071679:Glycogen Synthase Kinase 3 beta; D051057:Proto-Oncogene Proteins c-akt
Epithelial mesenchymal transition; Gastric cancer; Gastrokine-2; Metastasis