Immune response to bacteria induces dissemination of Ras-activated Drosophila hindgut cells

• Published in: EMBO reports 2012-06, Vol.13 (6), p.569-576
• Main Authors: Bangi, Erdem, Pitsouli, Chrysoula, Rahme, Laurence G, Cagan, Ross, Apidianakis, Yiorgos
• Format: Article
• Language: English
• Subjects: Amino Acid Substitution; Animals; Bacteria; c-Jun amino-terminal kinase; cancer; Cell Movement; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms; Disease Models, Animal; Drosophila; Drosophila - cytology; Drosophila - immunology; Drosophila - microbiology; Drosophila Proteins - genetics; Drosophila Proteins - metabolism; EMBO23; EMBO24; Epithelial Cells - metabolism; Epithelial Cells - microbiology; Epithelial Cells - physiology; Extracellular matrix; Gastrointestinal Tract - cytology; Gastrointestinal Tract - immunology; Gastrointestinal Tract - microbiology; Hindgut; Host-Pathogen Interactions; Immune response; Immunity, Innate; Immunology; Infection; innate immunity; Insects; Intestine; JNK Mitogen-Activated Protein Kinases - metabolism; Malignancy; Midgut; Mode of action; Molecular biology; Oncogene Proteins - genetics; Oncogene Proteins - metabolism; Oncogenes; Pathology; Pseudomonas aeruginosa; Pseudomonas aeruginosa - physiology; ras Proteins - genetics; ras Proteins - metabolism; Scientific Report; Scientific Reports; Signal Transduction; Synergism
• ISSN: 1469-221X; 1469-3178
• DOI: 10.1038/embor.2012.44

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 Ras1 V12 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 Ras1 V12 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. Drosophila hindgut cells exposed to bacterial infection activate the innate immune response. Concomitant expression of the Ras1V12 oncogene leads to extracellular matrix degradation, basal cell invasion and dissemination in the body cavity.