Nodal Promotes the Migration and Invasion of Bladder Cancer Cells via Regulation of Snail

Urinary bladder cancer is one of commonly diagnosed malignancies worldwide, especially in males. Understanding the mechanisms of advanced metastasis in bladder cell is important for therapy and drug development. Nodal, an important embryonic morphogen, has been reported to modulate tumorigenesis. We found that the expression of Nodal was upregulated in bladder cancer cells and tissues as compared to their corresponding controls. Knockdown of Nodal can suppress the migration, invasion, and epithelial-to-mesenchymal transition (EMT) of bladder cancer cells. Nodal can positively regulate the expression of Snail, one powerful EMT transcription factors, in bladder cancer cells. Overexpression of Snail can attenuate the si-Nodal suppressed cell migration and invasion. Nodal can increase the transcription and protein stability of Snail in bladder cancer cells. YY1, which can be activated by Nodal, is responsible for Nodal induced transcription of Snail. ATM, which can stabilize Snail by phosphorylation on Serine-100, was involved in Nodal upregulated protein stability of Snail. Collectively, our data showed that Nodal can trigger the malignancy of bladder cancer cells via increasing the transcription and protein stability of Snail. It indicated that Nodal might be a potential therapeutic target for bladder cancer treatment.