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Int J Biol Sci 2018; 14(3):280-293. doi:10.7150/ijbs.23756

Research Paper

Frizzled7 Promotes Epithelial-to-mesenchymal Transition and Stemness Via Activating Canonical Wnt/β-catenin Pathway in Gastric Cancer

Guanman Li1*, Qiao Su2*, Haibo Liu5, Dong Wang3, Wenhui Zhang4, Zhenhai Lu6, Yu Chen9, Xiaohui Huang1, Wen Li1, Changhua Zhang7, Yulong He7, Li Fu8, Jiong Bi1✉

1. Laboratory of General Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, Guangdong, China
2. Animal Center, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, Guangdong, China
3. Department of Clinical Laboratory, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, Guangdong, China
4. Department of Pathology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, Guangdong, China
5. Key Laboratory for Major Obstetric Diseases of Guangdong Province, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou 510000, Guangdong, China
6. Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, Guangzhou 510060, Guangdong, China
7. Gastrointestinal Surgery Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, Guangdong, China
8. Guangdong Key Laboratory for Genome Stability & Disease Prevention, Department of Pharmacology and Cancer Research Centre, School of Medicine, Shenzhen University, Shenzhen, China
9. Department of Immunity, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510080, Guangdong, China
* These authors contributed equally to the study.

Abstract

Aberrant activation of Wnt signaling is a crucial event in tumor development and metastasis. Wnt signaling is commonly divided into canonical and non-canonical signaling pathways based on whether β-catenin is activated (canonical). The two signaling pathways are initiated by Wnt ligand binding to the surface Frizzled (FZD) receptors, and regulate cancer stem cell self-renewal and epithelial-mesenchymal transition (EMT). Frizzled 7 (FZD7), a member of Frizzled family, promotes cell proliferation and invasiveness in many cancers, suggesting that FZD7 transmitting Wnt signaling is important for driving cancer growth. FZD7 expression has been reported to be up-regulated in human primary gastric cancer tissues. However, the molecular mechanism by which FZD7 promotes gastric cancer(GC) development and progression is not fully understood. Our present study showed that FZD7 was overexpressed in clinical GC samples, and thus was correlated with tumor invasion, lymphatic and organ metastasis, late TNM stages and poor patient survival. The endogenous expression of FZD7 was significantly increased in cancer stem cell-enriched spheres compared with adherent cells. Furthermore, RNA interference-mediated silencing of FZD7 inhibited proliferation, migration and invasion in gastric cancer cells. Moreover, ablation of FZD7 down-regulated EMT and the expression levels of cancer stem cell markers, and these inhibitions were associated with attenuated canonical Wnt/β-catenin signaling. The results suggest that Wnt canonical pathway may contribute to tumorigenesis and metastasis, indicating that FZD7 could be a potential therapeutic target for gastric cancer.

Keywords: FZD7, gastric cancer, cancer stem cell, epithelial-mesenchymal transition, Wnt/β-catenin pathway

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.
How to cite this article:
Li G, Su Q, Liu H, Wang D, Zhang W, Lu Z, Chen Y, Huang X, Li W, Zhang C, He Y, Fu L, Bi J. Frizzled7 Promotes Epithelial-to-mesenchymal Transition and Stemness Via Activating Canonical Wnt/β-catenin Pathway in Gastric Cancer. Int J Biol Sci 2018; 14(3):280-293. doi:10.7150/ijbs.23756. Available from http://www.ijbs.com/v14p0280.htm