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RORα Suppresses Epithelial-to-Mesenchymal Transition and Invasion in Human Gastric Cancer Cells via the Wnt/β-Catenin Pathway

Retinoid-related orphan receptor alpha (RORα) is involved in tumor development. However, the mechanisms underlying RORα inhibiting epithelial-to-mesenchymal transition (EMT) and invasion are poorly understood in gastric cancer (GC). This study revealed that the decreased expression of RORα is associ...

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Autores principales: Su, Jian, Su, Bo, Xia, Hong, Liu, Fang, Zhao, XiaoHong, Li, Juan, Zhang, JiZhen, Shi, Ying, Zeng, Ying, Zeng, Xi, Ling, Hui, Wu, YouHua, Su, Qi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6909819/
https://www.ncbi.nlm.nih.gov/pubmed/31867273
http://dx.doi.org/10.3389/fonc.2019.01344
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author Su, Jian
Su, Bo
Xia, Hong
Liu, Fang
Zhao, XiaoHong
Li, Juan
Zhang, JiZhen
Shi, Ying
Zeng, Ying
Zeng, Xi
Ling, Hui
Wu, YouHua
Su, Qi
author_facet Su, Jian
Su, Bo
Xia, Hong
Liu, Fang
Zhao, XiaoHong
Li, Juan
Zhang, JiZhen
Shi, Ying
Zeng, Ying
Zeng, Xi
Ling, Hui
Wu, YouHua
Su, Qi
author_sort Su, Jian
collection PubMed
description Retinoid-related orphan receptor alpha (RORα) is involved in tumor development. However, the mechanisms underlying RORα inhibiting epithelial-to-mesenchymal transition (EMT) and invasion are poorly understood in gastric cancer (GC). This study revealed that the decreased expression of RORα is associated with GC development, progression, and prognosis. RORα suppressed cell proliferation, EMT, and invasion in GC cells through inhibition of the Wnt/β-catenin pathway. RORα overexpression resulted in the decreased Wnt1 expression and the increased RORα interaction with β-catenin, which could lead to the decreased intranuclear β-catenin and p-β-catenin levels, concomitant with downregulated T-cell factor-4 (TCF-4) expression and the promoter activity of c-Myc. The inhibition of Wnt/β-catenin pathway was coupled with the reduced expression of Axin, c-Myc, and c-Jun. RORα downregulated vimentin and Snail and upregulated E-cadherin protein levels in vitro and in vivo. Inversely, knockdown of RORα attenuated its inhibitory effects on Wnt/β-catenin pathway and its downstream gene expression, facilitating cell proliferation, EMT, migration, and invasion in GC cells. Therefore, RORα could play a crucial role in repressing GC cell proliferation, EMT, and invasion via downregulating Wnt/β-catenin pathway.
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spelling pubmed-69098192019-12-20 RORα Suppresses Epithelial-to-Mesenchymal Transition and Invasion in Human Gastric Cancer Cells via the Wnt/β-Catenin Pathway Su, Jian Su, Bo Xia, Hong Liu, Fang Zhao, XiaoHong Li, Juan Zhang, JiZhen Shi, Ying Zeng, Ying Zeng, Xi Ling, Hui Wu, YouHua Su, Qi Front Oncol Oncology Retinoid-related orphan receptor alpha (RORα) is involved in tumor development. However, the mechanisms underlying RORα inhibiting epithelial-to-mesenchymal transition (EMT) and invasion are poorly understood in gastric cancer (GC). This study revealed that the decreased expression of RORα is associated with GC development, progression, and prognosis. RORα suppressed cell proliferation, EMT, and invasion in GC cells through inhibition of the Wnt/β-catenin pathway. RORα overexpression resulted in the decreased Wnt1 expression and the increased RORα interaction with β-catenin, which could lead to the decreased intranuclear β-catenin and p-β-catenin levels, concomitant with downregulated T-cell factor-4 (TCF-4) expression and the promoter activity of c-Myc. The inhibition of Wnt/β-catenin pathway was coupled with the reduced expression of Axin, c-Myc, and c-Jun. RORα downregulated vimentin and Snail and upregulated E-cadherin protein levels in vitro and in vivo. Inversely, knockdown of RORα attenuated its inhibitory effects on Wnt/β-catenin pathway and its downstream gene expression, facilitating cell proliferation, EMT, migration, and invasion in GC cells. Therefore, RORα could play a crucial role in repressing GC cell proliferation, EMT, and invasion via downregulating Wnt/β-catenin pathway. Frontiers Media S.A. 2019-12-06 /pmc/articles/PMC6909819/ /pubmed/31867273 http://dx.doi.org/10.3389/fonc.2019.01344 Text en Copyright © 2019 Su, Su, Xia, Liu, Zhao, Li, Zhang, Shi, Zeng, Zeng, Ling, Wu and Su. 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
Su, Jian
Su, Bo
Xia, Hong
Liu, Fang
Zhao, XiaoHong
Li, Juan
Zhang, JiZhen
Shi, Ying
Zeng, Ying
Zeng, Xi
Ling, Hui
Wu, YouHua
Su, Qi
RORα Suppresses Epithelial-to-Mesenchymal Transition and Invasion in Human Gastric Cancer Cells via the Wnt/β-Catenin Pathway
title RORα Suppresses Epithelial-to-Mesenchymal Transition and Invasion in Human Gastric Cancer Cells via the Wnt/β-Catenin Pathway
title_full RORα Suppresses Epithelial-to-Mesenchymal Transition and Invasion in Human Gastric Cancer Cells via the Wnt/β-Catenin Pathway
title_fullStr RORα Suppresses Epithelial-to-Mesenchymal Transition and Invasion in Human Gastric Cancer Cells via the Wnt/β-Catenin Pathway
title_full_unstemmed RORα Suppresses Epithelial-to-Mesenchymal Transition and Invasion in Human Gastric Cancer Cells via the Wnt/β-Catenin Pathway
title_short RORα Suppresses Epithelial-to-Mesenchymal Transition and Invasion in Human Gastric Cancer Cells via the Wnt/β-Catenin Pathway
title_sort rorα suppresses epithelial-to-mesenchymal transition and invasion in human gastric cancer cells via the wnt/β-catenin pathway
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6909819/
https://www.ncbi.nlm.nih.gov/pubmed/31867273
http://dx.doi.org/10.3389/fonc.2019.01344
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