Reference - Detail
|Author||Ohsawa S, Sugimura K, Takino K, Xu T, Miyawaki A, Igaki T.|
|Title||Elimination of oncogenic neighbors by JNK-mediated engulfment in Drosophila.|
A newly emerged oncogenic cell in the epithelial population has to confront antitumor selective pressures in the host tissue. However, the mechanisms by which surrounding normal tissue exerts antitumor effects against oncogenically transformed cells are poorly understood. In Drosophila imaginal epithelia, clones of cells mutant for evolutionarily conserved tumor suppressor genes such as scrib or dlg lose their epithelial integrity and are eliminated from epithelia when surrounded by wild-type tissue. Here, we show that surrounding normal cells activate nonapoptotic JNK signaling in response to the emergence of oncogenic mutant cells. This JNK activation leads to upregulation of PVR, the Drosophila PDGF/VEGF receptor. Genetic and time-lapse imaging analyses reveal that PVR expression in surrounding cells activates the ELMO/Mbc-mediated phagocytic pathway, thereby eliminating oncogenic neighbors by engulfment. Our data indicate that JNK-mediated cell engulfment could be an evolutionarily conserved intrinsic tumor-suppression mechanism that eliminates premalignant cells from epithelia.
|MeSH||Adaptor Proteins, Signal Transducing / genetics Adaptor Proteins, Signal Transducing / metabolism Animals Drosophila Proteins / genetics Drosophila Proteins / metabolism* Drosophila melanogaster / anatomy & histology* Drosophila melanogaster / embryology* Drosophila melanogaster / metabolism Enzyme Activation Epithelium / embryology Epithelium / metabolism JNK Mitogen-Activated Protein Kinases / genetics JNK Mitogen-Activated Protein Kinases / metabolism* Membrane Proteins / genetics Membrane Proteins / metabolism Neoplasms / pathology Neoplasms / physiopathology Oncogenes* Phagocytosis / physiology* Receptor Protein-Tyrosine Kinases / genetics Receptor Protein-Tyrosine Kinases / metabolism Recombinant Fusion Proteins / genetics Recombinant Fusion Proteins / metabolism Signal Transduction / physiology Tumor Suppressor Proteins / genetics Tumor Suppressor Proteins / metabolism|
|WOS Category||DEVELOPMENTAL BIOLOGY CELL BIOLOGY|