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A Drosophila APC tumour suppressor homologue functions in cellular adhesion

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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Figure 1: The N175K mutation and its phenotype in the ventral cuticle.
Figure 2: Delocalization of junctional Armadillo in N175K mutants.
Figure 3: Oocyte mislocalization in APC mutants.
Figure 4: Ultrastructural defects in adhesive membranes of N175K mutants.
Figure 5: E-APC is required for recovery of junctional Armadillo after actin depolymerization.

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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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