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Updated: Feb 3, 2026

3-D Cell Culture System for Studying Invasion and Evaluating Therapeutics in Bladder Cancer
Published on: September 13, 2018
Nodal regulates bladder cancer cell migration and invasion via the ALK/Smad signaling pathway
Youkong Li1, Wen Zhong2, Min Zhu1
1Department of Urology, Jingzhou Central Hospital and The Second Clinical Medical College, Yangtze University, Jingzhou 434020, People's Republic of China, yiukongli0412@163.com.
Background:
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.
Materials And Methods:
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.
Results:
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.
Conclusion:
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.
Insights
Nodal acts as an oncogene in bladder cancer, promoting cell proliferation and invasion. Inhibiting Nodal may offer a new treatment strategy for bladder cancer by targeting the ALK/Smad signaling pathway.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Bladder cancer is a prevalent urinary tract malignancy.
- The role and mechanisms of Nodal in bladder cancer remain largely unexplored.
Purpose of the Study:
- To investigate the biological function of Nodal in bladder cancer.
- To elucidate the molecular mechanisms underlying Nodal's role in bladder cancer progression.
Main Methods:
- Quantitative real-time PCR to assess Nodal expression in tissues and cells.
- In vitro assays (MTT, colony formation, transwell) to evaluate Nodal's impact on cell proliferation, migration, and invasion.
- Western blot to analyze protein expression related to proliferation, invasion, and the ALK/Smad signaling pathway.
Main Results:
- Nodal expression is significantly upregulated in bladder cancer.
- Nodal downregulation inhibits bladder cancer cell proliferation, clone formation, migration, and invasion.
- Nodal affects the expression of key proteins (CDC6, E-cadherin, MMP-2, MMP-9) and components of the ALK/Smad pathway (ALK4, ALK7, Smad2, Smad4).
- SB431542, an ALK4/7 inhibitor, reverses Nodal-induced pro-tumorigenic effects.
Conclusions:
- Nodal functions as an oncogene in bladder cancer.
- Nodal promotes bladder cancer progression by regulating proliferation, migration, and invasion through the ALK/Smad signaling pathway.
- Targeting Nodal and the ALK/Smad pathway presents a potential therapeutic strategy for bladder cancer.
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