A Protein Interaction between β-Catenin and Dnmt1 Regulates Wnt Signaling and DNA Methylation in Colorectal Cancer Cells

摘要: Aberrant activation of the Wnt signaling pathway is an important step in initiation and progression tumor development diverse cancers. The central effector canonical signaling, β-catenin (CTNNB1), a multifunctional protein, has been extensively studied with respect to its roles cell–cell adhesion regulation Wnt-driven transcription. Here, novel mass spectrometry–based proteomics technique colorectal cancer cells expressing stabilized β-catenin, was used identify protein–protein interaction between DNA methyltransferase I (Dnmt1) primary regulator methylation patterns mammalian cells. Dnmt1 strongly colocalized nuclei cells, mediated by domain protein. protein abundance dependent upon levels increased mutant β-catenin. Conversely, regulates nuclear β-catenin/TCF–driven In addition, lysine-specific demethylase 1 (LSD1/KDM1A), DNMT1 stability, identified as component Dnmt1–β-catenin complex perturbation altered methylation. summary, functional two critically oncoproteins, turn revealing link downstream functions Dnmt1. Implications: Two critical mutually regulate one each other9s activities Mol Cancer Res; 13(6); 969–81. ©2015 AACR.