title: Immune response to bacteria induces dissemination of Ras-activated Drosophila hindgut cells.
abstract: Although pathogenic bacteria are suspected contributors to colorectal cancer progression, cancer-promoting bacteria and their mode of action remain largely unknown. Here we report that sustained infection with the human intestinal colonizer Pseudomonas aeruginosa synergizes with the Ras1V12 oncogene to induce basal invasion and dissemination of hindgut cells to distant sites. Cross-talk between infection and dissemination requires sustained activation by the bacteria of the Imd-dTab2-dTak1 innate immune pathway, which converges with Ras1V12 signalling on JNK pathway activation, culminating in extracellular matrix degradation. Hindgut, but not midgut, cells are amenable to this cooperative dissemination, which is progressive and genetically and pharmacologically inhibitable. Thus, Drosophila hindgut provides a valuable system for the study of intestinal malignancies.
authors.affiliation: Department of Developmental and Regenerative Biology, Mount Sinai School of Medicine, New York, New York 10029, USA.
authors.forename: Erdem
authors.initials: E
authors.lastname: Bangi
authors.forename: Chrysoula
authors.initials: C
authors.lastname: Pitsouli
authors.forename: Laurence G
authors.initials: LG
authors.lastname: Rahme
authors.forename: Ross
authors.initials: R
authors.lastname: Cagan
authors.forename: Yiorgos
authors.initials: Y
authors.lastname: Apidianakis
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D002465:Cell Movement; D015179:Colorectal Neoplasms; D004195:Disease Models, Animal; D004330:Drosophila / Q000166:cytology / Q000276:immunology* / Q000382:microbiology; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism / Q000382:microbiology / Q000502:physiology; D041981:Gastrointestinal Tract / Q000166:cytology / Q000276:immunology* / Q000382:microbiology; D054884:Host-Pathogen Interactions; D007113:Immunity, Innate; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D011550:Pseudomonas aeruginosa / Q000502:physiology*; D015398:Signal Transduction; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D029721:Drosophila Proteins; D015513:Oncogene Proteins; D048031:JNK Mitogen-Activated Protein Kinases; C417283:Ras85D protein, Drosophila; D018631:ras Proteins