FZD7 is a novel prognostic marker and promotes tumor metastasis via WNT and EMT signaling pathways in esophageal squamous cell carcinoma
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Ting-Ting Cao1, Di Xiang1, Bei-Lei Liu1, Tu-Xiong Huang1, Bin-Bin Tan1, Chui-Mian Zeng1, Zhong-Yuan Wang1, Xiao-Yan Ming2, Li-Yi Zhang2, Guangyi Jin1, Feng Li3,4, Jian-Lin Wu5, Xin-Yuan Guan2, Desheng Lu1 and Li Fu1
1Department of Pharmacology and Cancer Research Centre, School of Medicine, Shenzhen University, Shenzhen, China
2Department of Clinical Oncology, The University of Hong Kong Faculty of Medicine, Hong Kong, China
3Wuhan University Shenzhen Research Institute, Shenzhen, China
4Department of Medical Genetics, School of Basic Medical Sciences, Wuhan University, Wuhan, China
5State Key Laboratory for Quality Research in Chinese Medicines, Macau University of Science and Technology, Macau, China
Li Fu, email: [email protected]
Desheng Lu, email: [email protected]
Keywords: FZD7, ESCC, metastasis, WNT, EMT
Received: May 24, 2017 Accepted: June 29, 2017 Published: July 26, 2017
Frizzled (FZD) proteins are receptors for secreted WNT proteins and play a critical role in the malignant progression of various cancers. However, the role of human FZD family members in esophageal squamous cell carcinoma (ESCC) was rarely investigated. In this study, we found that the FZD7 gene was the most commonly up-regulated FZD member in ESCC cell lines compared with other FZDs. TMA studies further validated that FZD7 protein was up-regulated in 165 of 252 (65.5%) informative ESCC patients and significantly correlated with poor overall survival (P=0.001). Additionally, multivariate Cox regression analysis showed that FZD7 overexpression was an independent prognostic factor for ESCC patients. Ectopic expression of FZD7 could promote ESCC cell metastasis both in vitro and in vivo. Under WNT3A stimulation, FZD7 was able to induce the nuclear translocation of β-catenin and activate the downstream targets of WNT/β-catenin signaling, as well as promote epithelial-mesenchymal transition (EMT) potential in ESCC cells. Our study demonstrated for the first time that FZD7 contributes to the malignant progression of ESCC and represents a novel prognostic marker and a potential therapeutic target for ESCC patients.
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