Cargando…

WNT2-Mediated FZD2 Stabilization Regulates Esophageal Cancer Metastasis via STAT3 Signaling

Esophageal cancer micro environment factor WNT2 was critical in cancer metastasis. However, very little is known about WNT2 receptors and their role in the malignant progression of ESCC. The clinical significance and underlying molecular mechanisms of FZD2, one of the receptors of WNT2, was further...

Descripción completa

Detalles Bibliográficos
Autores principales: Fu, Yufei, Zheng, Qi, Mao, Yingying, Jiang, Xiyi, Chen, Xin, Liu, Pei, Lv, Bin, Huang, Tuxiong, Yang, Jiao, Cheng, Yongran, Dai, Xiaoyi, Dai, Chunyan, Wang, Xi, Yin, Yifei, Song, Tengjiao, Jin, Weiyang, Zou, Chang, Chen, Tianhui, Fu, Li, Chen, Zhe
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7379028/
https://www.ncbi.nlm.nih.gov/pubmed/32766155
http://dx.doi.org/10.3389/fonc.2020.01168
_version_ 1783562551452237824
author Fu, Yufei
Zheng, Qi
Mao, Yingying
Jiang, Xiyi
Chen, Xin
Liu, Pei
Lv, Bin
Huang, Tuxiong
Yang, Jiao
Cheng, Yongran
Dai, Xiaoyi
Dai, Chunyan
Wang, Xi
Yin, Yifei
Song, Tengjiao
Jin, Weiyang
Zou, Chang
Chen, Tianhui
Fu, Li
Chen, Zhe
author_facet Fu, Yufei
Zheng, Qi
Mao, Yingying
Jiang, Xiyi
Chen, Xin
Liu, Pei
Lv, Bin
Huang, Tuxiong
Yang, Jiao
Cheng, Yongran
Dai, Xiaoyi
Dai, Chunyan
Wang, Xi
Yin, Yifei
Song, Tengjiao
Jin, Weiyang
Zou, Chang
Chen, Tianhui
Fu, Li
Chen, Zhe
author_sort Fu, Yufei
collection PubMed
description Esophageal cancer micro environment factor WNT2 was critical in cancer metastasis. However, very little is known about WNT2 receptors and their role in the malignant progression of ESCC. The clinical significance and underlying molecular mechanisms of FZD2, one of the receptors of WNT2, was further investigated in ESCC. We found that FZD2 expression was positively correlated with WNT2 levels in clinical ESCC specimens through database analysis. Upregulated FZD2 expression was detected in 69% (69/100) of the primary ESCC cases examined, and increased FZD2 expression was significantly correlated with poor prognosis (P < 0.05). Mechanistically, FZD2 induced the migration and invasion of ESCC cells by regulating the FZD2/STAT3 signaling. In vivo xenograft experiments further revealed the metastasis-promoting role of FZD2 in ESCC. Moreover, we found that the WNT2 ligand could stabilize and phosphorylate the FZD2 receptor by attenuating FZD2 ubiquitination, leading to the activation of STAT3 signaling and the initiation of ESCC cell metastasis. Collectively, our data revealed that a novel non-canonical WNT2/FZD2/STAT3 signaling axis is critical for ESCC progression. Strategies targeting this specific signaling axis might be developed to treat patients with ESCC.
format Online
Article
Text
id pubmed-7379028
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-73790282020-08-05 WNT2-Mediated FZD2 Stabilization Regulates Esophageal Cancer Metastasis via STAT3 Signaling Fu, Yufei Zheng, Qi Mao, Yingying Jiang, Xiyi Chen, Xin Liu, Pei Lv, Bin Huang, Tuxiong Yang, Jiao Cheng, Yongran Dai, Xiaoyi Dai, Chunyan Wang, Xi Yin, Yifei Song, Tengjiao Jin, Weiyang Zou, Chang Chen, Tianhui Fu, Li Chen, Zhe Front Oncol Oncology Esophageal cancer micro environment factor WNT2 was critical in cancer metastasis. However, very little is known about WNT2 receptors and their role in the malignant progression of ESCC. The clinical significance and underlying molecular mechanisms of FZD2, one of the receptors of WNT2, was further investigated in ESCC. We found that FZD2 expression was positively correlated with WNT2 levels in clinical ESCC specimens through database analysis. Upregulated FZD2 expression was detected in 69% (69/100) of the primary ESCC cases examined, and increased FZD2 expression was significantly correlated with poor prognosis (P < 0.05). Mechanistically, FZD2 induced the migration and invasion of ESCC cells by regulating the FZD2/STAT3 signaling. In vivo xenograft experiments further revealed the metastasis-promoting role of FZD2 in ESCC. Moreover, we found that the WNT2 ligand could stabilize and phosphorylate the FZD2 receptor by attenuating FZD2 ubiquitination, leading to the activation of STAT3 signaling and the initiation of ESCC cell metastasis. Collectively, our data revealed that a novel non-canonical WNT2/FZD2/STAT3 signaling axis is critical for ESCC progression. Strategies targeting this specific signaling axis might be developed to treat patients with ESCC. Frontiers Media S.A. 2020-07-16 /pmc/articles/PMC7379028/ /pubmed/32766155 http://dx.doi.org/10.3389/fonc.2020.01168 Text en Copyright © 2020 Fu, Zheng, Mao, Jiang, Chen, Liu, Lv, Huang, Yang, Cheng, Dai, Dai, Wang, Yin, Song, Jin, Zou, Chen, Fu and Chen. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Fu, Yufei
Zheng, Qi
Mao, Yingying
Jiang, Xiyi
Chen, Xin
Liu, Pei
Lv, Bin
Huang, Tuxiong
Yang, Jiao
Cheng, Yongran
Dai, Xiaoyi
Dai, Chunyan
Wang, Xi
Yin, Yifei
Song, Tengjiao
Jin, Weiyang
Zou, Chang
Chen, Tianhui
Fu, Li
Chen, Zhe
WNT2-Mediated FZD2 Stabilization Regulates Esophageal Cancer Metastasis via STAT3 Signaling
title WNT2-Mediated FZD2 Stabilization Regulates Esophageal Cancer Metastasis via STAT3 Signaling
title_full WNT2-Mediated FZD2 Stabilization Regulates Esophageal Cancer Metastasis via STAT3 Signaling
title_fullStr WNT2-Mediated FZD2 Stabilization Regulates Esophageal Cancer Metastasis via STAT3 Signaling
title_full_unstemmed WNT2-Mediated FZD2 Stabilization Regulates Esophageal Cancer Metastasis via STAT3 Signaling
title_short WNT2-Mediated FZD2 Stabilization Regulates Esophageal Cancer Metastasis via STAT3 Signaling
title_sort wnt2-mediated fzd2 stabilization regulates esophageal cancer metastasis via stat3 signaling
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7379028/
https://www.ncbi.nlm.nih.gov/pubmed/32766155
http://dx.doi.org/10.3389/fonc.2020.01168
work_keys_str_mv AT fuyufei wnt2mediatedfzd2stabilizationregulatesesophagealcancermetastasisviastat3signaling
AT zhengqi wnt2mediatedfzd2stabilizationregulatesesophagealcancermetastasisviastat3signaling
AT maoyingying wnt2mediatedfzd2stabilizationregulatesesophagealcancermetastasisviastat3signaling
AT jiangxiyi wnt2mediatedfzd2stabilizationregulatesesophagealcancermetastasisviastat3signaling
AT chenxin wnt2mediatedfzd2stabilizationregulatesesophagealcancermetastasisviastat3signaling
AT liupei wnt2mediatedfzd2stabilizationregulatesesophagealcancermetastasisviastat3signaling
AT lvbin wnt2mediatedfzd2stabilizationregulatesesophagealcancermetastasisviastat3signaling
AT huangtuxiong wnt2mediatedfzd2stabilizationregulatesesophagealcancermetastasisviastat3signaling
AT yangjiao wnt2mediatedfzd2stabilizationregulatesesophagealcancermetastasisviastat3signaling
AT chengyongran wnt2mediatedfzd2stabilizationregulatesesophagealcancermetastasisviastat3signaling
AT daixiaoyi wnt2mediatedfzd2stabilizationregulatesesophagealcancermetastasisviastat3signaling
AT daichunyan wnt2mediatedfzd2stabilizationregulatesesophagealcancermetastasisviastat3signaling
AT wangxi wnt2mediatedfzd2stabilizationregulatesesophagealcancermetastasisviastat3signaling
AT yinyifei wnt2mediatedfzd2stabilizationregulatesesophagealcancermetastasisviastat3signaling
AT songtengjiao wnt2mediatedfzd2stabilizationregulatesesophagealcancermetastasisviastat3signaling
AT jinweiyang wnt2mediatedfzd2stabilizationregulatesesophagealcancermetastasisviastat3signaling
AT zouchang wnt2mediatedfzd2stabilizationregulatesesophagealcancermetastasisviastat3signaling
AT chentianhui wnt2mediatedfzd2stabilizationregulatesesophagealcancermetastasisviastat3signaling
AT fuli wnt2mediatedfzd2stabilizationregulatesesophagealcancermetastasisviastat3signaling
AT chenzhe wnt2mediatedfzd2stabilizationregulatesesophagealcancermetastasisviastat3signaling