{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Jiang X"],"funding":["NICHD NIH HHS","NIMH NIH HHS"],"pagination":["529-41"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC2577847"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["13(6)"],"pubmed_abstract":["Genetic and epigenetic defects in Wnt/beta-catenin signaling play important roles in colorectal cancer progression. Here we identify DACT3, a member of the DACT (Dpr/Frodo) gene family, as a negative regulator of Wnt/beta-catenin signaling that is transcriptionally repressed in colorectal cancer. Unlike other Wnt signaling inhibitors that are silenced by DNA methylation, DACT3 repression is associated with bivalent histone modifications. Remarkably, DACT3 expression can be robustly derepressed by a pharmacological combination that simultaneously targets both histone methylation and deacetylation, leading to strong inhibition of Dishevelled (Dvl)-mediated Wnt/beta-catenin signaling and massive apoptosis of colorectal cancer cells. Our study identifies DACT3 as an important regulator of Wnt/"],"journal":["Cancer cell"],"pubmed_title":["DACT3 is an epigenetic regulator of Wnt/beta-catenin signaling in colorectal cancer and is a therapeutic target of histone modifications."],"pmcid":["PMC2577847"],"funding_grant_id":["R01 HD055300","K08 MH01750","K08 MH001750","1R01 HD055300"],"pubmed_authors":["Yang X","Kivimae S","Li J","Stanton LW","Cheyette BN","Tan J","Jiang X","Chan MT","Yu Q","Liu ET","Zhuang L","Lee PL"],"additional_accession":[]},"is_claimable":false,"name":"DACT3 is an epigenetic regulator of Wnt/beta-catenin signaling in colorectal cancer and is a therapeutic target of histone modifications.","description":"Genetic and epigenetic defects in Wnt/beta-catenin signaling play important roles in colorectal cancer progression. Here we identify DACT3, a member of the DACT (Dpr/Frodo) gene family, as a negative regulator of Wnt/beta-catenin signaling that is transcriptionally repressed in colorectal cancer. Unlike other Wnt signaling inhibitors that are silenced by DNA methylation, DACT3 repression is associated with bivalent histone modifications. Remarkably, DACT3 expression can be robustly derepressed by a pharmacological combination that simultaneously targets both histone methylation and deacetylation, leading to strong inhibition of Dishevelled (Dvl)-mediated Wnt/beta-catenin signaling and massive apoptosis of colorectal cancer cells. Our study identifies DACT3 as an important regulator of Wnt/","dates":{"release":"2008-01-01T00:00:00Z","publication":"2008 Jun","modification":"2026-05-05T05:00:02.895Z","creation":"2019-03-27T00:19:14Z"},"accession":"S-EPMC2577847","cross_references":{"pubmed":["18538736"],"doi":["10.1016/j.ccr.2008.04.019"]}}