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

Retinoid-related orphan receptor alpha (ROR alpha) is involved in tumor development. However, the mechanisms underlying ROR alpha inhibiting epithelial-to-mesenchymal transition (EMT) and invasion are poorly understood in gastric cancer (GC). This study revealed that the decreased expression of ROR alpha is associated with GC development, progression, and prognosis. ROR alpha suppressed cell proliferation, EMT, and invasion in GC cells through inhibition of the Wnt/beta-catenin pathway. ROR alpha overexpression resulted in the decreased Wnt1 expression and the increased ROR alpha interaction with beta-catenin, which could lead to the decreased intranuclear beta-catenin and p-beta-catenin levels, concomitant with downregulated T-cell factor-4 (TCF-4) expression and the promoter activity of c-Myc. The inhibition of Wnt/beta-catenin pathway was coupled with the reduced expression of Axin, c-Myc, and c-Jun. ROR alpha downregulated vimentin and Snail and upregulated E-cadherin protein levels in vitro and in vivo. Inversely, knockdown of ROR alpha attenuated its inhibitory effects on Wnt/beta-catenin pathway and its downstream gene expression, facilitating cell proliferation, EMT, migration, and invasion in GC cells. Therefore, ROR alpha could play a crucial role in repressing GC cell proliferation, EMT, and invasion via downregulating Wnt/beta-catenin pathway.