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

Abstract

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.

A gene signature driven by abnormally methylated DEGs was developed for TP53 wild-type ovarian cancer samples by integrative omics analysis of DNA methylation and gene expression data

“…Also, β1,6 N-acetylglucosaminyl transferase 2 (GCNT2) has been shown to promote the malignant progression of cancer as an oncogene in prostate cancer 26678556, breast cancer 21750175, esophageal cancer 30575058, and colon cancer 28542779, and as a tumor suppressor gene in melanoma cells. Furthermore, the Dapper antagonist of catenin-3 (DACT3) inhibits the malignant tumor phenotype in acute myeloid leukemia ( 42 ). Peptidase inhibitor 3 (PI3), often called elafin, is overexpressed and secreted in OC, and is related to the poor OS of OC and may be the determinant of the low survival rate of OC ( 43 ).…”