Abstract
Adenomatous polyposis coli (APC) is an important tumour suppressor in the intestinal epithelium. Its function in reducing nuclear β-catenin and T-cell factor (TCF)-mediated transcription is conserved from Drosophila to mammals. But APC proteins are also associated with the plasma membrane. Here, we show that mutational inactivation of Drosophila E-APC causes delocalization of Armadillo (the Drosophila β-catenin) but not DE-cadherin from adhesive plasma membranes. Extensive gaps between these membranes are visible at the ultrastructural level. The oocyte is also mislocalized in E-APC mutant egg chambers, a phenotype that results from a failure of cadherin-based adhesion. These results indicate that Drosophila APC functions in cellular adhesion; these results could have implications for colorectal adenoma formation and tumour progression in humans.
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Acknowledgements
We thank A. Bejsovec and E. Wieschaus for APC mutants, D. Kershaw for assistance with electron microscopy preparations, R. Rosin-Arbesfeld for transgenic flies expressing E-APC, T. Uemura and the Developmental Studies Hybridoma Bank for antibodies, J. Kilmartin and M. Robinson for advice with electron microscopy, and H. Pelham and M. Freeman for comments on the manuscript. F.H. was supported by the Uehara Memorial Foundation, Tokyo.
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Hamada, F., Bienz, M. A Drosophila APC tumour suppressor homologue functions in cellular adhesion. Nat Cell Biol 4, 208–213 (2002). https://doi.org/10.1038/ncb755
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DOI: https://doi.org/10.1038/ncb755
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