AEG-1 Induces Metastasis Of Gastric Cancer By Upregulation Of EIF4E Expression

Gastric cancer is one of the major malignant tumors threatening people's life.It is not only the second most common solid tumors in China,but the second most common causes of cancer-related death in China.Owing to the symptoms of early gastric carcinoma are not obvious,most patients are diagnosed at advanced stage with lymph node,peritoneal and distant metastasis,which is the main reason for its high mortility.AEG-1(astrocyte elevated gene-1)has been reported to promote several types of cancers;however,its mechanism hasn't been fully elucidated.In this study,we found that gain-of or lose-of function of AEG-1 promoted or suppressed the epithelial-mesenchymal transition(EMT),migration,and invasion of gastric cancer cell lines respectively,as well as regulated eIF4E,MMP-9,and Twist expression.Manipulating eIF4E expression by transfection of overexpression constructs or siRNAs not only partially eliminated AEG-1-regulated EMT,cell migration and invasion,but also turned over AEG-1-mediated MMP-9 and Twist expression.Moreover,overexpression or knockdown of eIF4E also promoted or repressed EMT,cell migration and invasion,in parallel with upregulation or downregulation of MMP-9 and Twist.Finally,knockdown of AEG-1 inhibited tumor growth in parallel with downregulation of eIF4E,MMP-9 and Twist in xenograft nude mouse model,as well as repressed lymphnode and peritoneal metastasis of gastric cancer in orthotopic nude mice model.Our results suggest that AEG-1 promotes the metastasis of gastric cancer through upregulation of eIF4E meditated MMP-9 and Twist expression.These findings provide a new mechanism for AEG-1-induced metastasis of gastric cancer,and a novel strategy for cancer therapy.