Requirement of cell cycle and apoptosis regulator 1 for target gene activation by Wnt and beta-catenin and for anchorage-independent growth of human colon carcinoma cells.

Aberrant Wnt signaling promotes oncogenesis by increasing cellular levels of beta-catenin, which associates with DNA-bound transcription factors and activates Wnt target genes. However, the molecular mechanism by which beta-catenin mediates gene expression is still poorly understood. Here, we show that cell cycle and apoptosis regulator 1 (CCAR1), which was recently ...
shown to function as a transcriptional coactivator for nuclear receptors, also interacts with beta-catenin and enhances the ability of beta-catenin to activate expression of transiently transfected reporter genes. Furthermore, association of CCAR1 with the promoter of an endogenous Wnt/beta-catenin target gene in a colon cancer cell line depends on the presence of beta-catenin. Depletion of CCAR1 inhibits expression of several Wnt/beta-catenin target genes and suppresses anchorage-independent growth of the colon cancer cell line. Thus, CCAR1 is a novel component of Wnt/beta-catenin signaling that plays an important role in transcriptional regulation by beta-catenin and that, therefore, may represent a novel target for therapeutic intervention in cancers involving aberrantly activated Wnt/beta-catenin signaling.
Mesh Terms:
Apoptosis Regulatory Proteins, Cell Adhesion, Cell Cycle Proteins, Cell Proliferation, Cell Transformation, Neoplastic, Colonic Neoplasms, Gene Expression Regulation, Neoplastic, HT29 Cells, Humans, Lymphoid Enhancer-Binding Factor 1, Protein Binding, Signal Transduction, Transcriptional Activation, Tumor Stem Cell Assay, Wnt Proteins, beta Catenin
J Biol Chem
Date: Jul. 31, 2009
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