Zhao Hongda, Bo Qiyu, Wang Weifen, Wang Rui, Li Yan, Chen Shouzhen, Xia Yangyang, Wang Wenfu, Wang Yong, Zhu Kejia, Liu Lei, Cui Jianfeng, Wang Shuai, Liu Qinggang, Wu Zonglong, Guo Hu, Shi Benkang
Department of Urology, Qilu Hospital of Shandong University, Jinan, China.
Department of First Operating Room, Qilu Hospital of Shandong University, Jinan, China.
J Cell Biochem. 2019 Feb;120(2):1979-1989. doi: 10.1002/jcb.27494. Epub 2018 Sep 19.
As an important chemokine receptor, the role of CCR4 in the progression of bladder cancer (BC) remains unknown. In this study, we have shown that CCR4 expression was upregulated in bladder carcinoma tissues compared with adjacent nontumor tissues. Kaplan-Meier survival analysis revealed that CCR4 expression was an independent prognostic risk factor in BC patients, and the addition of CCL17 induced CCR4 production and promoted migration and invasion of BC cells. In addition, CCR4 knockdown significantly attenuated the migratory and invasive capabilities of BC cells. Mechanistically, CCL17-CCR4 axis is involved in ERK1/2 signaling and could mediate the migration and invasion of BC cells by regulating MMP13 activation. This study suggests that CCR4 might represent a promising prognostic biomarker and a potential therapeutic option for BC.
作为一种重要的趋化因子受体，CCR4在膀胱癌（BC）进展中的作用尚不清楚。在本研究中，我们发现与相邻的非肿瘤组织相比，CCR4在膀胱癌组织中的表达上调。Kaplan-Meier生存分析显示，CCR4表达是BC患者的独立预后危险因素，添加CCL17可诱导CCR4产生并促进BC细胞的迁移和侵袭。此外，CCR4基因敲低显著减弱了BC细胞的迁移和侵袭能力。机制上，CCL17-CCR4轴参与ERK1/2信号传导，并可通过调节MMP13激活来介导BC细胞的迁移和侵袭。本研究表明，CCR4可能是一种有前景的预后生物标志物以及BC的潜在治疗靶点。
