Frizzled 8 promotes the cell proliferation and metastasis of renal cell carcinoma

// Qiwei Yang 1, 2, * , Ye Wang 3, * , Xiuwu Pan 1, 2, * , Jianqing Ye 1 , Sishun Gan 1 , Fajun Qu 1 , Lu Chen 4 , Chuanmin Chu 1 , Yi Gao 4 and Xingang Cui 1 1 Department of Urology, The Third Affiliated Hospital of Second Military Medical University (Eastern Hepatobiliary Surgery Hospital), Shanghai 201805, People’s Republic of China 2 Department of Urology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, People’s Republic of China 3 Department of Urology, Changhai Hospital, Second Military Medical University, Shanghai 200082, People’s Republic of China 4 Department of Urology, Ruijin Hospital, Shanghai Jiaotong University, Shanghai 200025, People’s Republic of China * These authors have contributed equally to this work Correspondence to: Xingang Cui, email: cuixingangjiaoshou@yeah.net Yi Gao, email: gaoyismmu@163.com Chuanmin Chu, email: drchucm@163.com Keywords: renal cell carcinoma, Wnt/β-catenin, Frizzled 8, proliferation, metastasis Received: October 31, 2016      Accepted: August 08, 2017      Published: September 08, 2017 ABSTRACT Recent reports have shown a rapid rise in the incidence of renal cell carcinoma (RCC), and Wnt (Wingless-related integration site) signaling pathway is important in RCC. Frizzled 8 (FZD8) is a member of Frizzled (FZD) receptor family which could activate canonical or non-canonical Wnt/β-catenin pathways. Nevertheless, the role of FZD8 in RCC is poorly investigated. The immunohistochemical analysis showed high expression of FZD8 in RCC tissues compared with peri-tumor tissues. FZD8 knockdown decreased the ability of proliferation and metastasis of RCC cells. Research revealed that the FZD8 regulated the transcription of Cyclin D1, c-Myc, and could promote the epithelial to mesenchymal transition (EMT) by mediating Vimentin and Snail through the Wnt/β-catenin signaling pathway. In addition, the results of our experiment revealed that FZD8 is involved in the regulation of non-canonical Wnt signaling pathway. These data suggested that the expression of FZD8 may play an important role in the proliferation and metastasis of RCC, and serve as a putative promising drug target for human RCC therapy.