ARHGEF40通过上皮间质转化促进结肠癌细胞侵袭

目的:研究鸟嘌呤核苷酸交换因子40(recombinant human rho guanine nucleotide exchange factor 40,ARHGEF40)对结肠癌细胞侵袭能力和上皮间质转化(epithelial-mesenchymal transition,EMT)标志蛋白表达的影响,探索ARHGE...

ARHGEF40 promotes colon cancer cell invasion through epithelial-mesenchymal transition

Objective:To investigate the effect of ARHGEF40 on the invasion of colon cancer cells and the expression of epithelial-mesenchymal transition marker proteins.To explore the mechanism via which ARHGEF40 regulates the invasion of colon cancer cells.Methods:Immunohistochemistry assay was performed to detect the expression of ARHGEF40 in colon cancer tissues and normal intestinal epithelial tissues.Transwell and Western blot assays were performed to determine the effect of ARHGEF40 overexpression and knockdown on colon cancer cells invasion and EMT marker protein expression.KEGG pathway enrichment analysis on the TCGA database was used to predict the possible mechanism of ARHGEF40 affecting the invasion of colon cells and EMT process.Results:Immunohistochemical analyses showed that the positive rate of ARHGEF40 in normal intestinal epithelial tissue was 22.2%(6/27),and in colon cancer tissue was 77.1%(37/48),which had a significant difference(P<0.01).Western blot results revealed that ARHGEF40 was highly expressed in four colon cancer cell lines compared to normal intestinal epithelial cell line.Transwell assays indicated that overexpression of ARHGEF40 significantly promoted the invasion of colon cancer cells CL187 and SW620,where as knockdown of ARHGEF40 significantly inhibited the invasion of these two cells(P<0.05).We also found that ARHGEF40 overexpression increased the expression of Snail,Slug,Vimentin,N-cadherin and decreased the expression of epithelioid marker protein E-cadherin in CL187 cell line.On the contrary,ARHGEF40 suppression downregulated the expression of Snail,Slug,Vimentin,N-cadherin and upregulated the expression of E-cadherin in SW620 cell line.Furthermore,enrichment analysis of KEGG signalling pathway showed that ARHGEF40 may activate TGF-β,WNT,NOTCH and MAPK signalling pathways in colon cancer.Conclusion:ARHGEF40 may promote the EMT and invasion of colon cancer cells by activating related signalling pathways.