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FZD5 prevents epithelial-mesenchymal transition in gastric cancer.
Dong, Dan; Na, Lei; Zhou, Kailing; Wang, Zhuo; Sun, Yu; Zheng, Qianqian; Gao, Jian; Zhao, Chenghai; Wang, Wei.
Afiliación
  • Dong D; Department of Pathophysiology, College of Basic Medical Science, China Medical University, Shenyang, People's Republic of China.
  • Na L; Department of Pathophysiology, College of Basic Medical Science, China Medical University, Shenyang, People's Republic of China.
  • Zhou K; Department of Urology, Shengjing Hospital of China Medical University, Shenyang, People's Republic of China.
  • Wang Z; Department of Pathophysiology, College of Basic Medical Science, China Medical University, Shenyang, People's Republic of China.
  • Sun Y; Department of Pathophysiology, College of Basic Medical Science, China Medical University, Shenyang, People's Republic of China.
  • Zheng Q; Department of Pathophysiology, College of Basic Medical Science, China Medical University, Shenyang, People's Republic of China.
  • Gao J; Department of Pathophysiology, College of Basic Medical Science, China Medical University, Shenyang, People's Republic of China.
  • Zhao C; Center of Laboratory Technology and Experimental Medicine, China Medical University, Shenyang, People's Republic of China.
  • Wang W; Department of Pathophysiology, College of Basic Medical Science, China Medical University, Shenyang, People's Republic of China. chzhao@cmu.edu.cn.
Cell Commun Signal ; 19(1): 21, 2021 02 22.
Article en En | MEDLINE | ID: mdl-33618713
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. Video Abstract.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Gástricas / Factores de Transcripción / Proteínas de Unión al ADN / Proteínas Proto-Oncogénicas c-ets / Receptores Frizzled / Transición Epitelial-Mesenquimal Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Cell Commun Signal Año: 2021 Tipo del documento: Article Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Gástricas / Factores de Transcripción / Proteínas de Unión al ADN / Proteínas Proto-Oncogénicas c-ets / Receptores Frizzled / Transición Epitelial-Mesenquimal Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Cell Commun Signal Año: 2021 Tipo del documento: Article Pais de publicación: Reino Unido