Discoidin domain receptor 1 activity drives an aggressive phenotype in bladder cancer.

Discoidin domain receptor 1 (DDR1) is a receptor tyrosine kinase which utilizes collagen as a ligand to regulate the interaction between cancer cells and tumor stroma. However, the clinical relevance of DDR1 expression in bladder cancer as well as its molecular regulation have not been previously investigated. Here, we assessed the role of DDR1 in bladder cancer. The DDR1 levels in bladder cancer specimens were examined by Western blot, compared to the paired adhesive normal controls. The effects of DDR1 were explored on both cell migration in bladder cancer cells and tumor growth as xenograft. We detected significant higher levels of DDR1 in bladder cancer tissues. Moreover, high levels of DDR1 were correlated with poor prognosis of corresponding patients. Both the in vitro cell invasiveness and in vivo tumor xenograft growth could be promoted by the overexpressed DDR1, while both of which could be inhibited after the depletion of DDR1. Furthermore, DDR1 increased the levels of ZEB1 and Slug, based on its effects on tumor invasion. In conclusion, DDR1 may promote the aggressiveness of bladder cancer cells and drive an aggressive phenotype in bladder cancer.