Dact3, short for Dapper antagonist of catenin-3, is a protein-coding gene. It is a negative regulator of the Wnt/β-catenin signaling pathway, which is crucial in many biological processes such as cell proliferation, differentiation, and apoptosis [1,2,3,4,6]. Dysregulation of this pathway is often associated with various diseases, especially cancers.

In acute myeloid leukemia (AML), low Dact3 levels are associated with shorter survival rates. Upregulation of Dact3 represses cellular proliferation, promotes cell cycle arrest and apoptosis of AML cells by decreasing levels of Dishevelled2 (DVL2), phospho-glycogen synthase kinase-3β (GSK-3β), and active β-catenin, thus suppressing Wnt/β-catenin-mediated transcriptional activity [1].

In non-small cell lung cancer (NSCLC), Dact3 expression is reduced, and its reduction is correlated with lymph node metastasis and poor prognosis. Dact3 may inhibit the malignant phenotype of NSCLC through downregulating c-Myb [3].

In glioma, a decrease in Dact3 expression is observed in tissues. Overexpression of Dact3 suppresses the proliferation, invasion, and migration of glioma cells, and increases cell adhesion by impeding the expression of notch 1 intracellular domain (NICD) and translocating into the nucleus by downregulating β-catenin, thereby suppressing Notch1 signaling [5].

In conclusion, Dact3 plays a significant tumor-suppressive role in multiple cancers, mainly through its regulation of the Wnt/β-catenin signaling pathway. Research on Dact3 knockout or conditional knockout mouse models could potentially further elucidate its role in these disease conditions, providing insights into cancer pathogenesis and potential therapeutic strategies.