title: A dual function of Drosophila capping protein on DE-cadherin maintains epithelial integrity and prevents JNK-mediated apoptosis.
abstract: E-cadherin plays a pivotal role in epithelial cell polarity, cell signalling and tumour suppression. However, how E-cadherin dysfunction promotes tumour progression is poorly understood. Here we show that the actin-capping protein heterodimer, which regulates actin filament polymerization, has a dual function on DE-cadherin in restricted Drosophila epithelia. Knocking down capping protein in the distal wing disc epithelium disrupts DE-cadherin and Armadillo localization at adherens junctions and upregulates DE-cadherin transcription. In turn, DE-cadherin provides an active signal, which prevents Wingless signalling and promotes JNK-mediated apoptosis. However, when cells are kept alive with the Caspase inhibitor P35, the activity of the JNK pathway and of the Yorkie oncogene trigger massive proliferation of cells that fail to stably retain associations with their neighbours. Moreover, loss of capping protein cooperates with the Ras oncogene to induce massive tissue overgrowth. Taken together, our findings argue that in some epithelia, the dual effect of capping protein loss on DE-cadherin triggers the elimination of mutant cells, preventing them from proliferating. However, the appearance of a second mutation that blocks cell death may allow for the development of some epithelial tumours.
authors.affiliation: Instituto Gulbenkian de Ciência, Rua da Quinta Grande 6, Oeiras, Portugal.
authors.forename: Barbara
authors.initials: B
authors.lastname: Jezowska
authors.forename: Beatriz García
authors.initials: BG
authors.lastname: Fernández
authors.forename: Ana Rita
authors.initials: AR
authors.lastname: Amândio
authors.forename: Paulo
authors.initials: P
authors.lastname: Duarte
authors.forename: Cláudia
authors.initials: C
authors.lastname: Mendes
authors.forename: Catarina
authors.initials: C
authors.lastname: Brás-Pereira
authors.forename: Florence
authors.initials: F
authors.lastname: Janody
mesh_terms: D051344:Actin Capping Proteins / Q000378:metabolism*; D022005:Adherens Junctions / Q000378:metabolism; D000818:Animals; D030801:Animals, Genetically Modified; D017209:Apoptosis; D051186:Armadillo Domain Proteins / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism*; D016764:Cell Polarity; D049109:Cell Proliferation; D002470:Cell Survival; D004330:Drosophila / Q000166:cytology / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D017344:Genes, Insect; D011905:Genes, ras; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008954:Models, Biological; D009154:Mutation; D009369:Neoplasms / Q000209:etiology / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014921:Wings, Animal / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D000091102:YAP-Signaling Proteins
chemical_list: C495305:ARM protein, Drosophila; D051344:Actin Capping Proteins; D051186:Armadillo Domain Proteins; D015820:Cadherins; C111891:DIAP1 protein, Drosophila; D029721:Drosophila Proteins; D051034:Inhibitor of Apoptosis Proteins; D009687:Nuclear Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins; C503814:Yki protein, Drosophila; C501889:shg protein, Drosophila; D048031:JNK Mitogen-Activated Protein Kinases