The adenosine A2b receptor promotes tumor progression of bladder urothelial carcinoma by enhancing MAPK signaling pathway.

The adenosine A2b receptor (A2bR) was considered to play an oncogenic role in many human malignancies. However, the expression and molecular function of A2bR in bladder urothelial carcinoma (BUC) have not been well elucidated. Herein, we found that the expression of A2bR was higher than other adenosine receptors in BUC tissues and cells, and it was upregulated in BUC tissues compared with matched normal bladder tissues. Furthermore, high expression of A2bR was associated with poor prognosis of patients with BUC. In addition, suppression of A2bR inhibited the proliferation, migration and invasion of BUC cells and arrested the cell cycle at the G1 phase. Finally, we demonstrated that downregulation of A2bR inhibited the proliferation, migration and invasion of BUC in part via the MAPK signaling pathway, increasing the levels of P21 but decreasing the levels of cyclin B1, D, E1, MMP-2 and MMP-9. Overexpression of MMP-2 could rescue BUC cells migration and invasion. Thus, the present study indicates that A2bR may play a potential oncogenic role in BUC progression and act as a potential biomarker to identify BUC patients with poor clinical outcomes.