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 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.
Highlights
Gastric cancer is the fifth most common malignancy and the third leading cause of cancer-related deaths worldwide [1]
Elevated expression of Astrocyte-elevated gene-1 (AEG-1) correlated with gastric cancer metastasis
We defined the role of AEG-1 in gastric cancer metastasis
Summary
Gastric cancer is the fifth most common malignancy and the third leading cause of cancer-related deaths worldwide [1]. The incidence and mortality rates of gastric cancer have decreased in recent years due to early diagnosis and considerable advances in surgical, chemo-, radio- and other adjuvant therapies, especially the treatment of Helicobacter pylori infections, the 5-year survival rate is still only 30% [2]. Most patients are diagnosed at a late stage with lymph node or distant metastases, or with relapse after prior curative surgical therapy [3]. AEG-1/ MTDH was subsequently found to mediate the metastasis of breast cancer [8]. AEG-1 expression was found to be elevated and correlated with clinical tumour type, stage, metastasis and prognosis in a variety of cancers, including breast [9], lung [10],
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
