Abstract
β-Catenin is a multi-functional protein involved in cell adhesion and signal transduction and has a critical role in colorectal cancer development. β-Catenin positively regulates the aryl-hydrocarbon receptor (AhR) mediated signal by both induction of AhR expression and enhancement of AhR-dependent gene induction. Conversely, it was reported that AhR negatively regulates the β-catenin signal via ubiquitination and subsequent degradation in a ligand dependent manner. However, there have been conflicting data among previous studies regarding the relationship between these two proteins. In this report, we conducted confirmatory studies dissecting the relationship between AhR and β-catenin. We did not observe β-catenin degradation by AhR ligands in several colon cancer cell lines. Reporter assays revealed that the AhR ligand did not alter TcF/β-catenin dependent transcription. Yeast and mammalian two-hybrid assays failed to reconstruct the interaction of β-catenin and AhR even when other factors, Arnt, CUL4B, and DDB1, were co-expressed additionally. Independently to induction of AhR expression, β-catenin enhanced AhR-dependent transcriptional activation via the xenobiotic response element (XRE). Coimmunoprecipitation detected the formation of a β-catenin and ligand-activated AhR complex, which was thought to reflect the β-catenin mediated enhancement of the AhR signaling. Overall, we could only confirm unidirectional interaction, which is positive regulation of the AhR signal by β-catenin. These results suggested that data from previous reports on the degradation of β-catenin via liganded AhR warrants further investigation to yield clarity in the field.
Highlights
Wnt family signals are triggered by extracellular glycolipoprotein and mediated by intracellular β-catenin. β-Catenin is a component of the cadherin protein complex that regulates cell– cell adhesion
We confirmed whether arylhydrocarbon receptor (AhR) ligands can reduce cytoplasmic β-catenin protein levels in colorectal adenocarcinoma DLD-1 cells, which were used previously [16]
We focused on ligand-dependent β-catenin degradation via AhR, and we attempted to verify previous data about AhR and β-catenin interactions
Summary
Wnt family signals are triggered by extracellular glycolipoprotein and mediated by intracellular β-catenin. β-Catenin is a component of the cadherin protein complex that regulates cell– cell adhesion. Intracellular quantity of β-catenin is well regulated by phosphorylation, and subsequent degradation is precisely executed by Axin, CK1, GSK-3β, and APC. The cytoplasmic β-catenin translocates into the nuclei, acts as a coactivator of Tcf/Lef family transcription factors, and activates the expression of Wnt/β-catenin target genes, including c-myc, axin, and cyclin D1. Those genes play important roles in tumorigenesis as well as cell proliferation [3,4]
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