CLCA4 inhibits bladder cancer cell proliferation, migration, and invasion by suppressing the PI3K/AKT pathway

// Teng Hou 1, * , Lijie Zhou 1, * , Longwang Wang 1, 2 , Gallina Kazobinka 1 , Xiaoping Zhang 1 and Zhaohui Chen 1 1 Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, China 2 Department of Urology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330008, China * These authors have contributed equally to this work Correspondence to: Zhaohui Chen, email: 1aiyan@sina.cn Keywords: CLCA4, bladder cancer, PI3K/Akt, proliferation, metastasis Received: July 21, 2017     Accepted: August 17, 2017     Published: October 09, 2017 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.