Nodal regulates bladder cancer cell migration and invasion via the ALK/Smad signaling pathway

Bladder cancer is the most common malignant tumor of the urinary tract. We aimed to explore the biological role and molecular mechanism of Nodal in bladder cancer. The expression of Nodal in bladder cancer tissues and cells was determined by quantitative real-time polymerase chain reaction. The effect of silencing of Nodal on cell proliferation, clone formation, and migration and invasion was evaluated by MTT cell proliferation assay, colony formation, and transwell assays, respectively. Western blot analysis was employed to detect the expression of proliferation- and invasion-related proteins and proteins involved in ALK/Smad signaling. We found that the expression of Nodal was significantly increased in bladder cancer tissues and cell lines. Downregulation of Nodal effectively weakened cell proliferation, clone formation, and cell migration and invasion abilities. The protein expression levels of CDC6, E-cadherin, MMP-2, and MMP-9 were also altered by downregulation of Nodal. Knockdown of Nodal also blocked the expression of ALK4, ALK7, Smad2, and Smad4, which are involved in ALK/Smad signaling. Additionally, the ALK4/7 receptor blocker SB431542 reversed the promotive effects of Nodal overexpression on bladder cancer cell proliferation, migration, and invasion. Our study indicated that Nodal functions as an oncogene by regulating cell proliferation, migration, and invasion in bladder cancer via the ALK/Smad signaling pathway, thereby providing novel insights into its role in bladder cancer treatment.