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

Qiwei Yang,Xiuwu Pan,Yi Gao,Sishun Gan,Xingang Cui,Lu Chen,Jianqing Ye,Ye Wang,Fajun Qu,Chuanmin Chu

doi:10.18632/oncotarget.20742

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.

Highlights

renal cell carcinoma (RCC) is the common type of malignant tumor in adult urologic neoplasms [1]
Frizzled 8 (FZD8) expression is increased in RCC tissues compared with peri-tumor tissues
It is urgent to probe the substantial cause of the metastatic initiation and development, which prevents the metastasis in the early stage of RCC progression

Summary

Introduction

RCC is the common type of malignant tumor in adult urologic neoplasms [1]. The incidence of RCC all over the world has been increasing in recent years [2]. The exact cause and mechanism of development of RCC remains unclear, so its pertinent to study its pathogenesis in greater detail for its eventual prevention and cure. The Wnt signaling pathway has been reported to play crucial role in the development of many tumors [3,4,5,6]. It is reported that von Hippel-lindau (VHL) tumor suppressor gene lost its function in familial and most sporadic clear cell RCC and upregulated β-catenin gives rise to renal carcinoma in mice [9]. Loss of VHL brings about activation of β-catenin by the HGF-driven, which is the degradation complex releasing β-catenin [10]

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