title: TC1 (C8orf4) enhances the Wnt/beta-catenin pathway by relieving antagonistic activity of Chibby.
abstract: The Wnt/beta-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 beta-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 beta-catenin target genes that are implicated in invasiveness and aggressive behavior of cancers, such as metalloproteinases, laminin gamma2, and others. Our data indicate that TC1 is a novel upstream regulator of the Wnt/beta-catenin pathway that enhances aggressive behavior of cancers.
authors.affiliation: Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, 388-1 Poongnap-Dong, Songpa-Gu, Seoul 138-736, Korea.
authors.forename: Yusun
authors.initials: Y
authors.lastname: Jung
authors.forename: Seunghyun
authors.initials: S
authors.lastname: Bang
authors.forename: Kyungho
authors.initials: K
authors.lastname: Choi
authors.forename: Eunsoon
authors.initials: E
authors.lastname: Kim
authors.forename: Youngmi
authors.initials: Y
authors.lastname: Kim
authors.forename: Jungtae
authors.initials: J
authors.lastname: Kim
authors.forename: Juhee
authors.initials: J
authors.lastname: Park
authors.forename: Hyunlyoung
authors.initials: H
authors.lastname: Koo
authors.forename: Randall T
authors.initials: RT
authors.lastname: Moon
authors.forename: Kyuyoung
authors.initials: K
authors.lastname: Song
authors.forename: Inchul
authors.initials: I
authors.lastname: Lee
mesh_terms: D002352:Carrier Proteins / Q000502:physiology*; D020869:Gene Expression Profiling; D006367:HeLa Cells; D006801:Humans; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000502:physiology*; D009687:Nuclear Proteins / Q000502:physiology*; D013274:Stomach Neoplasms / Q000473:pathology; D015854:Up-Regulation; D051153:Wnt Proteins / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism*
chemical_list: C473750:CBY1 protein, human; D002352:Carrier Proteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; C418741:TCIM protein, human; D051153:Wnt Proteins; D051176:beta Catenin