CXCR6 signaling promotes BrCa cell migration and invasion through Src, FAK, ERK1/2, and PI3K/Akt pathways. The addition of chemotactic gradients of CXCL16 resulted in the migration of CXCR6-expressing BrCa cells compared to untreated cells, as shown in Panel (A). Open and solid bars represent the results for MDA-MB-231 and MCF-7, respectively. Blocking of the chemokine and receptor interaction with anti-CXCR6 antibody reduced the migration of BrCa cells. Src (SU6656, 5 μM), FAK (PF-573228, 5 μM), and ERK inhibition also significantly reduced the migration of these cells. A significant number of MCF-7 (solid bar) and MDA-MB-231 (open bar) cells also invaded to the lower chamber towards higher CXCL16 in a CXCR6-dependent manner as shown in Panel (B). Inhibition of PI3Kp110α (PI-103, 3 μM), PI3Kp110β (TGX221, 1 μM), and PI3Kp110γ (AS605240, 3 μM), wortmannin (1 μM) impaired the CXCL16-led invasion of BrCa cells. Significant differences between groups were analyzed by student’s t-test using mean values obtained from three independent experiments (n = 3). For all tests, p values < 0.05 were considered significant. #, p-value < 0.05 compared to a vehicle-treated group of the corresponding cell line; **, p-value < 0.01 compared to the CXCL16 group of the corresponding cell line.