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J Cell Biochem. 2018 Sep 19. doi: 10.1002/jcb.27494. [Epub ahead of print]

CCL17-CCR4 axis promotes metastasis via ERK/MMP13 pathway in bladder cancer.

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Department of Urology, Qilu Hospital of Shandong University, Jinan, China.
Department of First Operating Room, Qilu Hospital of Shandong University, Jinan, China.


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.


C-C motif chemokine ligand 17; C-C motif chemokine receptor 4; bladder cancer (BC); invasion; migration


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