Astrocyte elevated gene-1 activates MMP9 to increase invasiveness of colorectal cancer.
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.
Department of Pathology, The Third Affiliated Hospital of Harbin Medical University, 150 Haping Road, Harbin, Heilongjiang Province, 150081, China.
Hongtao
H
Song
Zhennan
Z
Tian
Yu
Y
Qin
Guodong
G
Yao
Songbin
S
Fu
Jingshu
J
Geng
D015815:Cell Adhesion Molecules / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness / Q000235:genetics* / Q000473:pathology; D009362:Neoplasm Metastasis / Q000235:genetics; D011379:Prognosis; D015398:Signal Transduction
D015815:Cell Adhesion Molecules; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9