Wnt信号通路
上皮-间质转换
连环素
癌症研究
基因敲除
细胞生长
波形蛋白
化学
下调和上调
生物
细胞生物学
信号转导
细胞凋亡
免疫学
免疫组织化学
基因
生物化学
作者
Jian Su,Bo Su,Hong Xia,Fang Liu,Xiaohong Zhao,Juan Li,Ji-Zhen Zhang,Ying Shi,Ying Zeng,Xi Zeng,Hui Ling,Youhua Wu,Qi Su
标识
DOI:10.3389/fonc.2019.01344
摘要
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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