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J Cell Mol Med. 2017 Dec;21(12):3481-3493. doi: 10.1111/jcmm.13258. Epub 2017 Jun 29.

AEG-1 induces gastric cancer metastasis by upregulation of eIF4E expression.

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Department of Pharmacology, Nanjing Medical University, Nanjing, Jiangsu, China.
Department of General Surgery, Medical Oncology and Pathology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
Department of Basic Medicine, Kangda College of Nanjing Medical University, Lianyungang, Jiangsu, China.
Department of Pathology, Nanjing Medical University Affiliated Nanjing Hospital (Nanjing First Hospital), Nanjing, Jiangsu, China.


Gastric cancer is the third leading cause of cancer-related deaths worldwide, and patients with lymph node, peritoneal and distant metastasis have a poor prognosis. Overexpression of Astrocyte-elevated gene-1 (AEG-1) has been reported to be correlated with the progression and metastasis of gastric cancer. However, its mechanisms are quite unclear. In this study, we found that elevated expression of AEG-1 was correlated with metastasis in human gastric cancer tissues. Moreover, gain- or loss-of-function of AEG-1, respectively, promoted or suppressed epithelial-mesenchymal transition (EMT), migration and invasion of gastric cancer cells. AEG-1 positively regulated eIF4E, MMP-9 and Twist expression. Manipulating eIF4E expression by transfection of overexpression constructs or siRNAs partially eliminated AEG-1-regulated EMT, cell migration and invasion. In addition, overexpression or knockdown of eIF4E promoted or suppressed EMT, cell migration and invasion in parallel with upregulation of MMP-9 and Twist expression, while manipulating eIF4E expression partially abrogated AEG-1-induced MMP-9 and Twist. Finally, silencing of AEG-1 expression not only inhibited tumour growth in parallel with downregulation of eIF4E, MMP-9 and Twist expression in a xenograft nude mouse model, but also suppressed lymph node and peritoneal metastasis of gastric cancer in an orthotopic nude mouse model. These findings suggest that AEG-1 promotes gastric cancer metastasis through upregulation of eIF4E-mediated MMP-9 and Twist, which provides new diagnostic markers and therapeutic targets for cancer metastasis.


AEG-1; eIF4E; epithelial-mesenchymal transition; gastric cancer; metastasis

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