Methylation of DACT2 promotes breast cancer development by activating Wnt signaling

Breast cancer is the most common malignant tumor in women worldwide. To explore the role of DACT2 in breast cancer, 5 cell lines and 153 cases of primary cancer were studied. The expression of DACT2 was detected in BT474, MDA-MB-231 and BT549 cells, while no expression was found in MDA-MB-468 and HBL100 cells. Complete methylation of DACT2 was found in MDA-MB-468 and HBL100 cells, partial methylation was observed in BT474 and BT549 cells, and no methylation was detected in MDA-MB-231 cells. Restoration of DACT2 expression was induced by 5-Aza in MDA-MB-468 and HBL100 cells. DACT2 was methylated in 49.7% (76/153) of primary breast cancer samples. Methylation of DACT2 was significantly associated with tumor size (P < 0.05). Reduced DACT2 expression was significantly associated with promoter region methylation in primary breast cancer (P < 0.05). DACT2 suppressed breast cancer cell growth and induced G1/S phase arrest in breast cancer cells. DACT2 inhibited Wnt/β-catenin signaling in human breast cancer cells and suppressed breast cancer cell tumor growth in xenograft mice. In conclusion, our results demonstrate that DACT2 is frequently methylated in human breast cancer, methylation of DACT2 activates Wnt signaling, and DACT2 suppresses breast cancer cell growth both in vitro and in vivo.