RSPO3 promotes the aggressiveness of bladder cancer via Wnt/β-catenin and Hedgehog signaling pathways.

R-spondin 3 (RSPO3) is a secreted protein that associates directly with Wnt/β-catenin signaling. However, its functional contribution and prognostic value in human bladder cancer remain unclear. Here, we showed that RSPO3 is upregulated in bladder cancer tissues and cells, and high expression of RSPO3 correlates with advanced clinicopathological features, poor prognosis and disease progression in bladder cancer patients. Furthermore, we observed that ectopic expression or knockdown of RSPO3 profoundly promoted or inhibited, respectively, the invasive ability of bladder cancer cells. Mechanistically, RSPO3 promoted bladder cancer progression via mediating the Wnt/β-catenin and Hedgehog signaling pathways. These findings demonstrate, for the first time, that RSPO3 exhibited a tumor-promoting effect in bladder cancer cells through activation of Wnt/β-catenin and Hedgehog signaling pathways. Thus, RSPO3 may be served as a potential therapeutic target for bladder cancer treatment.