Knockdown of MMP‑1 inhibits the progression of colorectal cancer by suppressing the PI3K/Akt/c‑myc signaling pathway and EMT.

Abstract

The present study aimed to investigate the role of matrix metalloproteinase-1 (MMP-1) in the development of colorectal cancer and reveal the mechanism underlying this progression. Bioinformatics methods and a public dataset were first used to analyze MMP-1 gene expression in a public dataset. MMP-1 expression in colorectal cancer patients was assessed by immunohistochemistry; its association with clinicopathological parameters and its significance for prognosis were analyzed. Then proliferation, scratch and Transwell assays and a xenograft model were used to assess the change in malignant behavior in cells transfected with an MMP-1 shRNA. Changes involved in epithelial-mesenchymal transition (EMT) and the Akt signaling pathway were detected by western blotting. According to the results, MMP-1 expression was higher in colorectal cancer tissues than it was in matched adjacent noncancerous tissues, and its high expression was significantly related to lymphatic metastasis as well as TNM stage (P<0.05). Downregulation of MMP-1 expression inhibited the progression of colorectal cancer in vitro and in vivo. Furthermore, after the cells were stably transfected with MMP-1 shRNA, the expression of N-cadherin, vimentin and Twist1 decreased while that of E-cadherin increased. The expression of p-Akt and c-Myc also decreased. In conclusion, MMP-1 may promote malignant behavior in colorectal cancer via EMT and the Akt signaling pathway.