A Drosophila APC tumour suppressor homologue functions in cellular adhesion.
Adenomatous polyposis coli (APC) is an important tumour suppressor in the intestinal epithelium. Its function in reducing nuclear beta-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 beta-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.
Hamada
Fumihiko
F
MRC Laboratory of Molecular Biology, Hills Road, Cambridge, CB2 2QH, UK.
Bienz
Mariann
M
D011125:Adenomatous Polyposis Coli / Q000209:etiology / Q000235:genetics; D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics / Q000502:physiology; D000595:Amino Acid Sequence; D000818:Animals; D051186:Armadillo Domain Proteins; D015820:Cadherins / Q000378:metabolism; D002448:Cell Adhesion / Q000235:genetics*; D004330:Drosophila / Q000166:cytology / Q000196:embryology / Q000235:genetics* / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000502:physiology; D005260:Female; D017491:Genes, APC; D017344:Genes, Insect; D006801:Humans; D019476:Insect Proteins / Q000378:metabolism; D008969:Molecular Sequence Data; D009865:Oocytes / Q000166:cytology; D010641:Phenotype; D017354:Point Mutation; D017386:Sequence Homology, Amino Acid; D015534:Trans-Activators; D014157:Transcription Factors
C495305:ARM protein, Drosophila; D025601:Adenomatous Polyposis Coli Protein; D051186:Armadillo Domain Proteins; D015820:Cadherins; D029721:Drosophila Proteins; D019476:Insect Proteins; D015534:Trans-Activators; D014157:Transcription Factors