DACT3, also known as disheveled binding antagonist of beta catenin 3, is a key negative regulator of the Wnt/β -catenin signaling pathway [1,2,3,4,5,6]. This pathway is crucial for numerous biological processes such as cell proliferation, differentiation, and development, and its dysregulation is associated with various diseases, especially cancers.

In acute myeloid leukemia (AML), upregulation of DACT3 in AML cells effectively repressed cellular proliferation, promoted cell cycle arrest and apoptosis. It decreased levels of Dishevelled2 (DVL2), phospho-glycogen synthase kinase-3β (GSK-3β), and active β-catenin, suppressing Wnt/β-catenin-mediated transcriptional activity. Overexpression of DACT3 also impeded the formation and growth of AML-derived xenograft tumors [1].

In non-small cell lung cancer (NSCLC), Dact3 expression was reduced, and its transfection led to decreased c-Myb expression, decreased Wnt/β-catenin signaling activity, and reduced cell invasive and proliferative capacity [3].

In glioma, overexpression of DACT3 significantly suppressed the proliferation, invasion, and migration of glioma cells, while increasing cell adhesion, through inhibiting the Notch1 signaling pathway in a β-catenin-dependent manner [6].

In conclusion, DACT3 plays a tumor-suppressive role in multiple cancers, mainly through its negative regulation of the Wnt/β-catenin signaling pathway. Studies using in vivo models like xenograft tumor mouse models in AML, NSCLC, and glioma have been crucial in revealing these functions, providing potential targets for cancer treatment.