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

Abstract

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.

Gamma linolenic acid suppresses hypoxia-induced gastric cancer cell growth and epithelial-mesenchymal transition by inhibiting the Wnt/b-catenin signaling pathway

“…Scutellarin reversed hypoxia-induced EMT in breast cancer cells through the PI3K/Akt and MAPK pathways [34]. Besides, it is also reported that Wnt signaling pathway promotes tumor progression and metastasis in various cancers [41]. Previous studies have shown that the Wnt/b-catenin pathway is activated in gastric cancer [42], and contributes to tumor malignancy in gastrointestinal stromal tumor [43].…”

Regulation of Wnt Signaling through Ubiquitination and Deubiquitination in Cancers

“…Also, in melanomas it is known that Axin1 regulates the level of β-catenin that has a synergy effect with a BRAF-V600E inhibitor (PLX4720) [51]. Recently, polymorphisms of the Axin1 gene were found to be associated with bladder cancer risk [52]. Axin2 has opposing functions in cancers.…”

Manifestation of Pathological States of Numerous Diseases in the Largest Organ of the Human Body: (II) From Pancreatitis to Pancreatic Cancer Invasion, Formation of Stroma around the Primary Tumor in the Fascia, to Early Detection of Non-Coding microRNAs in Body Fluids and Development of Drugs to Treat Different Stages of Pancreatic Cancer

“…In 2012, a novel mechanism for the stabilization of p53 protein expression via activation of the orphan nuclear receptor-RORα was introduced [77]. Figure S1B, C) of [78]). It has been found that overexpression of RORα could inhibit the proliferation, EMT, and invasion of these cells [78].…”

“…Figure S1B, C) of [78]). It has been found that overexpression of RORα could inhibit the proliferation, EMT, and invasion of these cells [78]. It has been pointed out that stimulation of G-protein-coupled receptors by glucagon or epinephrine activates Lats1/2 kinase activity, thereby inhibiting the YAP function [79].…”