SPAG9 regulates HEF1 expression and drives EMT in bladder transitional cell carcinoma via rac1 signaling pathway.

Recently SPAG9 has been reported to show aberrant expressions in numerous human malignancies and act as a crucial role in tumor's proliferation and invasion. Human enhancer of filamentation 1 (HEF1, also known as CasL and NEDD9) is a non-catalytic scaffolding protein belonging to CAS (Crk-associated substrate) protein family that interacts with multiple signaling cascades. Due to the diversified function of HEF1, abnormal expression of HEF1 frequently combines with malignant phenotypes and poor prognosis. However, little is known between the relationship of SPAG9 and HEF1 in bladder tumorigenesis. In this study, expression of SPAG9 in vivo and in vitro has been detected by quantitative real-time PCR and Western blot analysis after transfected with SPAG9 overexpression/inhibitor vector. We also found that HEF1 expression shows consistency and is regulated by SPAG9. Overexpression of SPAG9 promotes bladder cancer cells migration through HEF1 upregulation and emerges protein level of activated Rac1. Silencing SPAG9 inhibits cell migration through HEF1 downregulation and reduces protein level of activated Rac1. Also, we found that expression of EMT marker such as E-cadherin, Vimentin is regulated by SPAG9. Considering EMT plays a crucial role in tumor cells spreading and invasion, SPAG9 and HEF1 may potentially set a new therapeutic approach to bladder cancer treatment.