DACT3 has a tumor-inhibiting role in acute myeloid leukemia via the suppression of Wnt/β-catenin signaling by DVL2.

Dapper antagonist of catenin-3 (DACT3) is a new tumor-related protein associated with a diverse set of tumors. However, whether DACT3 plays a role in acute myeloid leukemia (AML) is not fully understood. Our findings showed low DACT3 level in AML tissue, which was corrected with shorter survival rates. Upregulation of DACT3 effectively repressed cellular proliferation, and promoted cell cycle arrest and apoptosis of AML cells. Upregulation of DACT3 decreased levels of Dishevelled2 (DVL2), phospho-glycogen synthase kinase-3β (GSK-3β), and active β-catenin, which collectively suppressed Wnt/β-catenin-mediated transcriptional activity. Overexpression of DVL2 reversed DACT3-mediated suppression of Wnt/β-catenin pathway. Reactivation of Wnt/β-catenin abrogated DACT3-upregulation-evoked tumor-suppression in AML cells. Overexpression of DACT3 impeded the formation and growth of AML-derived xenograft tumor. Collectively, our work reveals a tumor-suppressive role of DACT3, a protein that negatively adjusts Wnt/β-catenin pathway via downregulation of DVL2 in AML.