FZD5 prevents epithelial-mesenchymal transition in gastric cancer

被引：28

作者：

Dong, Dan ^{[1
]}

Na, Lei ^{[1
,2
]}

Zhou, Kailing ^{[1
]}

Wang, Zhuo ^{[1
]}

Sun, Yu ^{[1
]}

Zheng, Qianqian ^{[1
]}

Gao, Jian ^{[3
]}

Zhao, Chenghai ^{[1
]}

Wang, Wei ^{[1
]}

机构：

[1] China Med Univ, Coll Basic Med Sci, Dept Pathophysiol, Shenyang, Peoples R China

[2] China Med Univ, Shengjing Hosp, Dept Urol, Shenyang, Peoples R China

[3] China Med Univ, Ctr Lab Technol & Expt Med, Shenyang, Peoples R China

来源：

CELL COMMUNICATION AND SIGNALING | 2021年 / 19卷 / 01期

基金：

中国博士后科学基金;

关键词：

FZD5; Epithelial-mesenchymal transition; ELF3; Gastric cancer;

D O I：

10.1186/s12964-021-00708-z

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Background: Frizzled (FZD) proteins function as receptors for WNT ligands. Members in FZD family including FZD2, FZD4, FZD7, FZD8 and FZD10 have been demonstrated to mediate cancer cell epithelial-mesenchymal transition (EMT). Methods: CCLE and TCGA databases were interrogated to reveal the association of FZD5 with EMT. EMT was analyzed by investigating the alterations in CDH1 (E-cadherin), VIM (Vimentin) and ZEB1 expression, cell migration and cell morphology. Transcriptional modulation was determined by ChIP in combination with Real-time PCR. Survival was analyzed by Kaplan-Meier method. Results: In contrast to other FZDs, FZD5 was identified to prevent EMT in gastric cancer. FZD5 maintains epithelial-like phenotype and is negatively modulated by transcription factors SNAI2 and TEAD1. Epithelial-specific factor ELF3 is a downstream effecter, and protein kinase C (PKC) links FZD5 to ELF3. ELF3 represses ZEB1 expression, further guarding against EMT. Moreover, FZD5 signaling requires its co-receptor LRP5 and WNT7B is a putative ligand for FZD5. FZD5 and ELF3 are associated with longer survival, whereas SNAI2 and TEAD1 are associated with shorter survival. Conclusions: Taken together, FZD5-ELF3 signaling blocks EMT, and plays a potential tumor-suppressing role in gastric cancer.

引用

页数：13

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