Chibby suppresses growth of human SW480 colon adenocarcinoma cells through inhibition of β-catenin signaling
1 Graduate Program in Molecular and Cellular Pharmacology, Stony Brook University, BST 7-186, Nicolls Rd, Stony Brook, NY, 11794-8651, USA
2 Department of Pharmacological Sciences, Stony Brook University, BST 7-168, Nicolls Rd, Stony Brook, NY, 11794-8651, USA
Journal of Molecular Signaling 2012, 7:6 doi:10.1186/1750-2187-7-6Published: 31 May 2012
The canonical Wnt signaling pathway is crucial for embryonic development and adult tissue homeostasis. Activating mutations in the Wnt pathway are frequently associated with the pathogenesis of various types of cancer, particularly colon cancer. Upon Wnt stimulation, β-catenin plays a central role as a coactivator through direct interaction with Tcf/Lef transcription factors to stimulate target gene expression. We have previously shown that the evolutionarily conserved protein Chibby (Cby) physically binds to β-catenin to repress β-catenin-dependent gene activation by 1) competing with Tcf/Lef factors for binding to β-catenin and 2) facilitating nuclear export of β-catenin via interaction with 14-3-3 proteins. In this study, we employed human colon adenocarcinoma SW480 cells with high levels of endogenous β-catenin to address a potential tumor suppressor role of Cby. In SW480 stable cells expressing wild-type Cby (CbyWT), but not 14-3-3-binding- defective Cby mutant CbyS20A, a significant fraction of endogenous β-catenin was detected in the cytoplasm. Consistent with this, CbyWT-expressing cells showed low levels of β-catenin signaling activity, leading to reduced growth. Our results suggest that Cby, in collaboration with 14-3-3 proteins, can counteract oncogenic β-catenin signaling in colon cancer cells.