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, data about the role of SVIL in the migration of colorectal cancer cells are scarce. 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. SVIL-knockdown HCT116/DDP cells with virus infection were also used. Migration was assessed by transwell assay and wound healing assay, 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 their parental cells. Also, the HCT116/DDP cells showed increased cell migration, stemness and lung metastasis. Furthermore, we revealed that the up-regulated SVIL was associated with the induction of migration of HCT116/DDP cells. Reduced SVIL expression reversed the enhanced migration and lung metastasis in cisplatin-resistant colorectal cancer cells. Further work showed that SVIL silencing reduced cell migration by targeting zona occludens (ZO)-1 mediated tight-junction remodeling. The expression of ZO-1, but not occludin and cludin5, was down-regulated after SVIL knock-down. Fluorescence detection indicated that the linear ZO-1 expression was interrupted in HCT116/DDP cells while the SVIL silencing reversed the interruption. This study firstly 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.