Supervillin-Mediated ZO-1 Downregulation Facilitates Migration of Cisplatin-Resistant HCT116 Colorectal Cancer Cells.

Abstract

Supervillin (SVIL), the biggest member of the villin/gelsolin superfamily, has recently been reported to promote the metastasis of hepatocellular carcinoma by stimulating epithelial-mesenchymal transition (EMT). However, little is known about the roles of SVIL in the migration of colorectal cancer cells. Here, we investigated the effects of SVIL on the migration of cisplatin-resistant colorectal cancer cells. The model of cisplatin-resistant HCT116 cells (HCT116/DDP) was established. Migration was assessed after SVIL knockdown. Tumor metastasis was assessed using a mouse model with tail vein injection of colorectal cancer cells. The results showed that the expression of SVIL was upregulated in HCT116/DDP cells compared to that in their parental cells. Also, the HCT116/DDP cells showed increased cell migration and lung metastasis. Furthermore, we revealed that the expression of SVIL was associated with the migration of HCT116/DDP cells. Reduced SVIL expression inhibited migration and lung metastasis in HCT116/DDP cells. Further work showed that SVIL knockdown blocked cell migration by targeting zona occludens-1 (ZO-1) mediated tight-junction remodeling. The expression of ZO-1, but not occludin and cludin5, was downregulated after SVIL knockdown. Immunofluorescence indicated that the linear ZO-1 was interrupted while the SVIL knockdown reversed the interruption. This study displayed the relationship between SVIL and ZO-1 in cisplatin-resistant colon cancer cells, providing a new insight into the mechanism of colorectal cancer migration.