Popis: |
The Wnt/β-catenin pathway has been implicated in human cancers. Here, we show that TC1 (C8orf4), a small protein present in vertebrates, functions as a positive regulator of the pathway. TC1 interacts with Chibby (Cby) and thereby enhances the signaling pathway by relieving the antagonistic function of Cby on the β-catenin–mediated transcription. Upon coexpression in mammalian cells, TC1 redistributes from nucleolus to nuclear speckles, where it colocalizes with Cby. TC1 up-regulates the expression of β-catenin target genes that are implicated in invasiveness and aggressive behavior of cancers, such as metalloproteinases, laminin γ2, and others. Our data indicate that TC1 is a novel upstream regulator of the Wnt/β-catenin pathway that enhances aggressive behavior of cancers. (Cancer Res 2006; 66(2): 723-8) |