Abstract
Adenosine 5'-triphosphate (ATP) is one of the most abundant biochemical constituents within the tumor microenvironment and is postulated to play critical roles in the progression of a number of types of tumors via interaction with the P2Y2 receptor. In the present study, we demonstrated that the P2Y2 receptor was highly expressed in MCF7 and Hs578T breast cancer cells. Downregulation of the P2Y2 receptor by small interfering RNA (siRNA) significantly attenuated ATP- or UTP-driven migration and invasion of the breast cancer cells as well as expression of EMT-related genes Snail and E-cadherin. Consistent with the observations in vitro, the P2Y2 receptor was found to be abundantly expressed at the invasive edge of the tumor, in infiltrating tumor cells in breast adipose tissues and/or the cancer embolus in the lymphatic sinuses compared with the tumor core areas. Furthermore, high Snail expression and weak or negative expression of E-cadherin were observed at the invasive edge of tumors. Taken together, these data indicate that the P2Y2 receptor promoted cell migration and invasion in breast cancer cells via EMT-related genes Snail and E-cadherin.