Taken together, our findings suggest for the first time that MDA-MB-231 highly metastatic breast cancer cells release higher levels of ATP and show higher P2Y2R activity in comparison to MCF-7 low metastatic breast cancer cells, and that ATP-mediated activation of P2Y2R plays an important role in cancer metastasis by modulating crosstalk between cancer cells and ECs. This evidence concerns the gene P2RY2 and breast carcinoma.