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.