TC1 (C8orf4) enhances the Wnt/beta-catenin pathway by relieving antagonistic activity of Chibby.
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.
Jung
Yusun
Y
Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, 388-1 Poongnap-Dong, Songpa-Gu, Seoul 138-736, Korea.
Bang
Seunghyun
S
Choi
Kyungho
K
Kim
Eunsoon
E
Kim
Youngmi
Y
Kim
Jungtae
J
Park
Juhee
J
Koo
Hyunlyoung
H
Moon
Randall T
RT
Song
Kyuyoung
K
Lee
Inchul
I
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*
C473750:CBY1 protein, human; D002352:Carrier Proteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; C418741:TCIM protein, human; D051153:Wnt Proteins; D051176:beta Catenin