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TC1 (C8orf4) Enhances the Wnt/ß-Catenin Pathway by Relieving Antagonistic Activity of Chibby

¹ Asan Institute for Life Sciences and Departments of ² Pathology and Biochemistry and ³ Molecular Biology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea; and ⁴ Howard Hughes Medical Institute, Department of Pharmacology, and Center for Developmental Biology, University of Washington School of Medicine, Seattle, Washington

Requests for reprints: Inchul Lee, Department of Pathology, University of Ulsan College of Medicine, 388-1 Poongnap-Dong, Songpa-Gu, Seoul 138-736, Korea. Phone: 82-2-3010-4551; Fax: 82-2-472-7898; E-mail: iclee{at}amc.seoul.kr.

The Wnt/ß-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 ß-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 ß-catenin target genes that are implicated in invasiveness and aggressive behavior of cancers, such as metalloproteinases, laminin 2, and others. Our data indicate that TC1 is a novel upstream regulator of the Wnt/ß-catenin pathway that enhances aggressive behavior of cancers. (Cancer Res 2006; 66(2): 723-8)

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