MORC2/β-catenin signaling axis promotes proliferation and migration of breast cancer cells.

Although Microrchidia 2 (MORC2) is overexpressed in many types of human cancer, its role in breast cancer progression remains unknown. Here, we report that the chromatin remodeler MORC2 expression positively correlates with β-catenin expression in breast cancer cell lines and patients. Overexpression of MORC2 augmented the expression of β-catenin and its target genes, cyclin D1 and c-Myc. Consistent with these results, we found MORC2 knockdown resulted in decreased expression of β-catenin and its target genes. Surprisingly, we observed that c-Myc, the target gene of β-catenin, regulated the MORC2-β-catenin signaling axis through a feedback mechanism. We demonstrated that MORC2 regulates β-catenin expression and function by modulating the phosphorylation of AKT. In addition, we observed reduced proliferation and migration of MORC2 overexpressing breast cancer cells upon β-catenin inhibition. Overall, our results demonstrate that MORC2 promotes breast cancer cell proliferation and migration by regulating β-catenin signaling.