FZD5 prevents epithelial-mesenchymal transition in gastric cancer

Cell Communication and Signaling

Jian Gao¹  Kailing Zhou²  Dan Dong²  Qianqian Zheng²  Wei Wang²  Chenghai Zhao²  Zhuo Wang²  Yu Sun²  Lei Na³ 

[1] Center of Laboratory Technology and Experimental Medicine, China Medical University, Shenyang, People’s Republic of China;Department of Pathophysiology, College of Basic Medical Science, China Medical University, Shenyang, People’s Republic of China;Department of Pathophysiology, College of Basic Medical Science, China Medical University, Shenyang, People’s Republic of China;Department of Urology, Shengjing Hospital of China Medical University, Shenyang, People’s Republic of China;

关键词: FZD5;    Epithelial-mesenchymal transition;    ELF3;    Gastric cancer;   

DOI  :  10.1186/s12964-021-00708-z

来源: Springer

【 摘 要 】

BackgroundFrizzled (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).MethodsCCLE 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.ResultsIn 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.ConclusionsTaken together, FZD5-ELF3 signaling blocks EMT, and plays a potential tumor-suppressing role in gastric cancer.CvvYPCxja5mx9fTex68jtmVideo Abstract

【 授权许可】

CC BY