Hou Teng, Zhou Lijie, Wang Longwang, Kazobinka Gallina, Zhang Xiaoping, Chen Zhaohui
Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, China.
Department of Urology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330008, China.
Oncotarget. 2017 Oct 9;8(54):93001-93013. doi: 10.18632/oncotarget.21724. eCollection 2017 Nov 3.
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.
钙激活氯离子通道A4（CLCA4）作为一种肿瘤抑制因子，已被证明与多种人类癌症的进展有关，但其在膀胱癌中的作用仍不清楚。在本研究中，我们发现与相邻的非肿瘤组织和正常尿路上皮细胞相比，CLCA4在膀胱癌组织和细胞中的表达下调。CLCA4低表达与膀胱癌患者的肿瘤体积较大、肿瘤分期较晚及预后较差相关。CLCA4的过表达显著减弱了膀胱癌细胞的增殖、生长、迁移和侵袭能力，而CLCA4基因敲低则产生相反的效果。从机制上讲，CLCA4参与PI3K/AKT信号传导，其下游分子可促进膀胱癌细胞增殖。此外，CLCA4可通过调节上皮-间质转化和PI3K/Akt激活来介导膀胱癌细胞的迁移和侵袭。本研究表明，CLCA4可能是一种有前景的膀胱癌预后生物标志物，并为膀胱癌的生长和侵袭提供了一种可能的机制。
