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SPAG9 regulates HEF1 expression and drives EMT in bladder transitional cell carcinoma via rac1 signaling pathway
Xu Li1, Fuquan Jiang1, Xinsheng Wang2
1Department of Urology, China-Japan Union Hospital of Jilin University Changchun 130033, Jilin, China.
Abstract:
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.
Insights
Aberrant expression of SPAG9 promotes bladder cancer cell migration by upregulating HEF1 and activating Rac1. This suggests SPAG9 and HEF1 as potential therapeutic targets for bladder cancer.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Aberrant expression of SPAG9 is implicated in various human malignancies.
- Human enhancer of filamentation 1 (HEF1) is a scaffolding protein involved in signaling cascades, with abnormal expression linked to poor prognosis.
- The relationship between SPAG9 and HEF1 in bladder cancer remains largely unexplored.
Purpose of the Study:
- To investigate the role of SPAG9 in bladder tumorigenesis.
- To elucidate the relationship between SPAG9 and HEF1 expression and function in bladder cancer cells.
- To explore the potential of SPAG9 and HEF1 as therapeutic targets.
Main Methods:
- Quantitative real-time PCR and Western blot analysis were used to detect SPAG9 and HEF1 expression in vitro and in vivo.
- SPAG9 overexpression and inhibitor vectors were utilized to modulate SPAG9 levels.
- Expression of epithelial-mesenchymal transition (EMT) markers and activated Rac1 protein levels were assessed.
Main Results:
- SPAG9 expression was found to be consistent with and regulated by HEF1.
- Overexpression of SPAG9 enhanced bladder cancer cell migration via HEF1 upregulation and increased activated Rac1 protein levels.
- Silencing SPAG9 inhibited cell migration, downregulated HEF1, and reduced activated Rac1 protein levels.
- SPAG9 was found to regulate EMT markers, including E-cadherin and Vimentin.
Conclusions:
- SPAG9 plays a crucial role in promoting bladder cancer cell migration and invasion through the HEF1/Rac1 pathway.
- SPAG9 influences epithelial-mesenchymal transition (EMT) markers, suggesting its involvement in tumor cell spreading.
- SPAG9 and HEF1 represent potential novel therapeutic targets for bladder cancer treatment.
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