Interestingly, these tumor cells establish functional GJICs with endothelial cells in vitro, and this process seems to be necessary for spheroid formation and colonization in 3D matrices (41), suggesting that Cx43 and Cx26 mediate breast cancer cell and melanoma metastasis to the brain via tumor-endothelial cell GJ-dependent mechanisms. This evidence concerns the gene GJA1 and breast cancer.