CXCR6 mediates migration and invasion of breast cancer cells in a Src, FAK, and ERK1/2 dependent fashion (133.6)

Abstract

Abstract Standard treatment modalities for breast cancer has improved the outlook for women afflicted with it. However, 40% of breast cancer patients still die from the disease, primarily due to metastasis. In this regard, chemokines and their corresponding receptor interactions in metastasis is an area of intense pre-clinical and clinical research. Our lab has demonstrated higher expression of CXCR6 in breast cancer cell lines (MCF-7 and MDA-MB-231) compared to the normal mammary epithelial cell line (MCF-10A), and expression by breast cancer tissue. We investigated the role of CXCR6 in breast cancer cell migration and invasion, which are key steps used by cancer cells to achieve metastatic goals. Breast cancer cells showed higher migratory and invasive potential towards the chemotactic gradients of CXCL16, which was significantly inhibited after CXCR6 blockade. Because our antibody array data showed phosphorylation of Src, FAK, and ERK1/2 in breast cancer cells following CXCL16 treatment, we used inhibitors against these molecules after CXCL16 treatment to determine the molecular mechanisms by which CXCR6 mediates migration and invasion. The results showed a significant decrease in migration and invasion, a reduction in F-actin polymerization, and decreased phosphorylation of Vav1, ezrin, cortactin, and paxillin. Taken together, this data suggests that Src, FAK, and ERK1/2 are required for CXCR6-mediated migration and invasion.