MACC1 promotes the invasion and migration of colorectal cancer through activating HGF/C-MET pathway
- VernacularTitle:MACC1激活HGF/c-MET通路促进结直肠癌侵袭迁移的机制研究
- Author:
Man XIONG
1
;
Yibing TAN
;
Ming YANG
;
Xiaoning SUN
;
Side LIU
;
Yang SONG
Author Information
- Publication Type:Journal Article
- Keywords: colorectal cancer; metastasis-associated in colon cancer-1(MACC1); hepatocyte growth factor(HGF); cellular-mesenchymal to epithelial transition factor(c-MET); invasion; migration
- From: Journal of Xi'an Jiaotong University(Medical Sciences) 2025;46(1):86-93
- CountryChina
- Language:Chinese
- Abstract: Objective To investigate the role and mechanism of metastasis-associated protein in colorectal cancer 1(MACC1)in the proliferation and migration of colorectal cancer.Methods The expression of MACC1 in colorectal cancer samples and para-cancerous samples from TCGA database was analyzed.The survival difference between the groups with high and low expression of MACC1 was studied.HCT116 cells were divided into Vector group(no treatment group)and MACC1 OE group(transfected with pcDNA3.1-MACC1 plasmid),si-NC group(negative control group),and si-MACC1 group(transfected with MACC1 siRNA).MTT assay was used to detect cell viability;EDU and cell clonal formation assay were used to detect cell proliferation.The migration and invasion of cells were detected by scratch and invasion assays,respectively.The mRNA expression level of cellular-mesenchymal epithelial transition factor(c-MET)was detected by RT-qPCR,and the protein expression of MACC1 and c-MET was detected by Western blotting.Colon cancer cell HCT116 transfected with MACC1 OE was inoculated subcutaneously into nude mice to establish tumor model,and the volume and weight of tumor tissue were measured.Results The expression level of MACC1 was upregulated in colorectal cancer tissue and cells(P＜0.05).Patients with high MACC1 expression had shorter overall survival than those with low MACC1 expression(P=0.003).Overexpression of MACC1 significantly increased cell viability(F=86.070,P＜0.001).Compared with those in si-NC group,the proliferation rate,migration,invasion and number of clone formation of HCT116 in si-MACC1 group were significantly decreased(P＜0.01).The expression of MACC1 protein was positively correlated with the expression of c-MET protein in colorectal cancer(r=0.802,P=0.002).Overexpression of MACC1 promoted the c-MET expression(t=13.532,P＜0.001),while knockdown of MACC1 inhibited the c-MET expression(t=14.626,P＜0.001).Luciferase reports assay demonstrated that c-MET was a transcriptional target of MACC1.MACC1 overexpression increased the tumor volume and weight of nude mice(P＜0.01).Conclusion MACC1 can promote the invasion and migration of colorectal cancer through hepatocyte growth factor/c-MET pathway.
