Inhibitors of Gq signalling down-regulate β-catenin expression & function in human colon cancer cells

BACKGROUND & OBJECTIVES: β-catenin signalling plays a key role in maintaining normal cellular physiology, and therefore, its deregulation can lead to many human diseases including cancers. Previously, we have shown that the activation of Gq signalling positively regulates β-catenin by inhibiting glycogen synthase kinase-3 beta and increasing the stability of β-catenin protein, however, these results were mainly based on overexpression experiments in either Xenopus oocytes or HEK293T cells. The present study was undertaken to evaluate the modulation of Gq signalling in human colon cancer cells. METHODS: Gq signalling in SW480 and HT-29 colon cancer cells was specifically blocked to investigate the interaction between β-catenin and the Gq signalling pathways. GP antagonist-2A (a commercially available peptide) and a minigene expression construct encoding a peptide corresponding to the C-terminal 11 amino acids of Gαq were used to block Gq signalling. β-catenin expression and function were examined by western blotting, immunofluorescence microscopy, and quantitative real-time PCR experiments. RESULTS: Transfection of cells with either of the blockers significantly decreased both β-catenin protein levels and β-catenin-mediated transcriptional activities. In addition, the migration of SW480 cells was reduced in the presence of the Gq blockers. INTERPRETATION & CONCLUSIONS: The results of this study further support the positive role of Gq signalling in regulating β-catenin expression and function and may provide a new means of preventing β-catenin-mediated carcinogenesis by blocking heterotrimeric G proteins.