title: Src controls tumorigenesis via JNK-dependent regulation of the Hippo pathway in Drosophila.
abstract: Cell-cell interactions within the tumour microenvironment have crucial roles in epithelial tumorigenesis. Using Drosophila genetics, we show that the oncoprotein Src controls tumour microenvironment by Jun N-terminal kinase (JNK)-dependent regulation of the Hippo pathway. Clones of cells with elevated Src expression activate the Rac-Diaphanous and Ras-mitogen-activated protein kinase (MAPK) pathways, which cooperatively induce F-actin accumulation, thereby leading to activation of the Hippo pathway effector Yorkie (Yki). Simultaneously, Src activates the JNK pathway, which antagonizes the autonomous Yki activity and causes propagation of Yki activity to neighbouring cells, resulting in the overgrowth of surrounding tissue. Our data provide a mechanism to explain how oncogenic mutations regulate tumour microenvironment through cell-cell communication.
authors.affiliation: Division of Genetics, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Enomoto
authors.forename: Tatsushi
authors.initials: T
authors.lastname: Igaki
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002450:Cell Communication; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D007814:Larva / Q000235:genetics / Q000378:metabolism*; D048670:MAP Kinase Kinase 4 / Q000235:genetics / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D008954:Models, Biological; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D059016:Tumor Microenvironment; D000091102:YAP-Signaling Proteins; D019061:src-Family Kinases / Q000235:genetics / Q000378:metabolism*; D000099317:Hippo Kinases
chemical_list: D000199:Actins; D029721:Drosophila Proteins; D047908:Intracellular Signaling Peptides and Proteins; D048670:MAP Kinase Kinase 4; D020928:Mitogen-Activated Protein Kinases; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases; D015534:Trans-Activators; D000091102:YAP-Signaling Proteins; D019061:src-Family Kinases; C503814:Yki protein, Drosophila; C499474:hpo protein, Drosophila; D000099317:Hippo Kinases