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Published on: September 13, 2018
CLCA4 inhibits bladder cancer cell proliferation, migration, and invasion by suppressing the PI3K/AKT pathway
Teng Hou1, Lijie Zhou1, Longwang Wang1,2
1Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, China.
Abstract:
Calcium activated chloride channel A4 (CLCA4), a tumor suppressor, was shown to contribute to the progression of several human cancers, while its role in bladder carcinoma remains unclear. In this study, we showed CLCA4 expression was down-regulated in bladder carcinoma tissues and cells compared to adjacent non-tumor tissues and normal urothelial cells. Low CLCA4 expression was correlated with larger tumor size, advanced tumor stage, and poor prognosis in bladder carcinoma patients. Overexpression of CLCA4 profoundly attenuated the proliferation, growth, migratory and invasive capabilities of bladder cancer cells, whereas CLCA4 knockdown had the opposite effect. Mechanistically, CLCA4 is involved in PI3K/AKT signaling and its downstream molecules can promote bladder cancer cell proliferation. Additionally, CLCA4 could mediate the migration and invasion of bladder cancer cells by regulating epithelial-mesenchymal transition and PI3K/Akt activation. This study suggests that CLCA4 may represent a promising prognostic biomarker for bladder cancer and provides a possible mechanism for bladder cancer growth and invasion.
Insights
Calcium activated chloride channel A4 (CLCA4) is down-regulated in bladder cancer, suppressing tumor growth and invasion. CLCA4 may serve as a prognostic biomarker for bladder carcinoma.
Area of Science:
- Oncology
- Molecular Biology
- Urology
Background:
- Calcium activated chloride channel A4 (CLCA4) is a known tumor suppressor in various cancers.
- Its specific role in bladder carcinoma progression and its potential as a biomarker are not well-defined.
Purpose of the Study:
- To investigate the expression and function of CLCA4 in bladder carcinoma.
- To determine the prognostic value of CLCA4 in bladder cancer patients.
- To elucidate the molecular mechanisms underlying CLCA4's role in bladder cancer.
Main Methods:
- Analysis of CLCA4 expression in bladder carcinoma tissues and cells.
- Correlation of CLCA4 expression with clinical parameters (tumor size, stage, prognosis).
- In vitro studies involving CLCA4 overexpression and knockdown to assess effects on cell proliferation, migration, and invasion.
- Investigation of CLCA4's involvement in PI3K/AKT signaling and epithelial-mesenchymal transition (EMT).
Main Results:
- CLCA4 expression was significantly downregulated in bladder carcinoma tissues and cells.
- Low CLCA4 expression correlated with larger tumor size, advanced stage, and poorer prognosis.
- CLCA4 overexpression inhibited bladder cancer cell proliferation, migration, and invasion.
- CLCA4 knockdown promoted these cancer cell behaviors.
- CLCA4 was found to be involved in PI3K/AKT signaling and EMT, influencing bladder cancer progression.
Conclusions:
- CLCA4 acts as a tumor suppressor in bladder carcinoma.
- CLCA4 expression levels can serve as a prognostic biomarker for bladder cancer.
- CLCA4 influences bladder cancer growth and invasion through the PI3K/AKT pathway and EMT regulation.
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