Journal
TUMOR BIOLOGY
Volume 35, Issue 7, Pages 6679-6685Publisher
SAGE PUBLICATIONS LTD
DOI: 10.1007/s13277-014-1883-3
Keywords
Astrocyte elevated gene-1 (AEG-1); Colorectal cancer; MMP9; Cancer invasiveness; Cancer metastasis
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Funding
- Third Affiliated Hospital of Harbin Medical University, China
- Wu Lien-Teh Science Foundation for Youths of Harbin Medical University [WLD-QN1117]
- Foundation of Heilongjiang Educational Committee [12511175]
- Scientific Research Staring Foundation
- Affiliated TumorHospital of Harbin Medical University [JJ 2010-13]
- Specialized Research Fund for the Doctoral Program of Higher Education [20122307120026]
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The molecular mechanism underlying the invasiveness of colorectal cancer (CRC) cells remains largely unknown. Here, we found that astrocyte elevated gene-1 (AEG-1) was significantly upregulated in CRC tissues, compared with the adjacent normal tissues from human patients. Ectopic expression of AEG-1 enhanced the invasive ability of CRC cells, while small interfering RNA (siRNA)-induced knockdown of AEG-1 inhibited the invasive ability of CRC cells. Transcription, protein levels, and secretion of matrix metalloproteinase 9 (MMP9), all increased by AEG-1 overexpression in CRC cells, and all decreased by AEG-1 inhibition. Suppression of endogenous MMP9 abrogated the effects of AEG-1 on invasiveness, without affecting AEG-1 levels. Taken together, these findings suggest that AEG-1 contributes to CRC invasiveness and metastasis by enhancing MMP9 activity. Thus, AEG-1 appears to be a novel therapeutic target for preventing the metastasis of CRC.
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