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.

Network pharmacology and molecular docking study on the mechanism of colorectal cancer treatment using Xiao-Chai-Hu-Tang

“…Previous studies have shown that baicalein could inhibit MMP-1 expression [ 27 ], and our study verified that bicycling and MMP-1 exhibit high binding energy through molecular docking. However, the downregulation of MMP‑1 expression inhibited the progression of colorectal cancer [ 28 ], it could thus be speculated that baicalein could slow down the progression of colorectal cancer by inhibiting MMP-1 expression. Kaempferol exhibits strong cytotoxic, anti-oxidant, anti-proliferative, and anti-apoptotic effects against HCT-116, HCT-15, SW480, and other CRC cells [ 29 ], and could also be used alone or combined with 5-FU to overcome CRC drug resistance [ 30 ].…”

“…Besides, CA 2 overexpression can improve the CRC cells’ sensitivity to chemotherapy drugs, which may be a potential biomarker for early CRC diagnosis [ 38 ]. Research shows that the expression of MMP-1 in colorectal cancer tissues is higher than that in normal colon tissues, and MMP-1 may influence the occurrence and development of colorectal cancer through EMT and Akt signaling pathways [ 28 ]. In conclusion, the targets of the XCHT active ingredients interact with the disease targets of CRC, giving full play to the unique advantages of multi-compounds and multi-targets of traditional Chinese medicine to prevent and treat CRC.…”

Comprehensive Proteomic Analysis of Colon Cancer Tissue Revealed the Reason for the Worse Prognosis of Right-Sided Colon Cancer and Mucinous Colon Cancer at the Protein Level

“…Matrix metalloproteinase-1 (MMP-1), also known as collagenase-1, has been demonstrated to mediate the pathological progression of diverse cancers [ 72 , 73 , 74 ]. Wang et al demonstrated that MMP-1 knockdown suppressed the progression of CRC by inhibiting the PI3K/Akt/c-myc signaling pathway and EMT [ 75 ]. All these results indicate that ECM-related EMT and IL-17 signaling pathways are strongly associated with the poor prognosis of right-sided colon cancers.…”

Discovery of potential drugs to treat aggressive pituitary adenomas through text mining

“…An increase in the CXCL8 level in the tumor microenvironment can promote the development of bladder cancer, and promote the angiogenesis and proliferation of tumor cells [18]. MMP1 is a mesenchymal collagen in the extracellular matrix, which involved in tumor behavior, and can promote the occurrence and metastasis of colorectal cancer through endothelial-mesenchymal transition and the protein kinase B signaling pathway [19]. ALB has an antioxidant effect in the blood vessels of people suffering from benign paroxysmal positional vertigo (BPPV), and a decrease in the serum level of ALB is related to BPPV pathogenesis [20].…”