Open AccessAEG ‐1 induces gastric cancer metastasis by upregulation of eIF 4E expression
Author(s) -
Wu Shengjie,
Yang Li,
Wu Dandan,
Gao Zhongyuan,
Li Ping,
Huang Wenbin,
Wang Xuerong
Publication year - 2017
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.13258
Subject(s) - downregulation and upregulation , cancer research , gene silencing , metastasis , cancer , cancer cell , gene knockdown , epithelial–mesenchymal transition , medicine , biology , pathology , cell culture , gene , biochemistry , genetics
Abstract 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 eIF 4E, MMP ‐9 and Twist expression. Manipulating eIF 4E expression by transfection of overexpression constructs or si RNA s partially eliminated AEG ‐1‐regulated EMT , cell migration and invasion. In addition, overexpression or knockdown of eIF 4E promoted or suppressed EMT , cell migration and invasion in parallel with upregulation of MMP ‐9 and Twist expression, while manipulating eIF 4E 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 eIF 4E, 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 eIF 4E‐mediated MMP ‐9 and Twist, which provides new diagnostic markers and therapeutic targets for cancer metastasis.