RRC ID 21852
著者 Enomoto M, Igaki T.
タイトル Src controls tumorigenesis via JNK-dependent regulation of the Hippo pathway in Drosophila.
ジャーナル EMBO Rep
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.
巻・号 14(1)
ページ 65-72
公開日 2013-1-1
DOI 10.1038/embor.2012.185
PII embor2012185
PMID 23196366
PMC PMC3537139
MeSH Actins / genetics Actins / metabolism Animals Cell Communication Cell Transformation, Neoplastic / genetics Cell Transformation, Neoplastic / metabolism Cells, Cultured Drosophila Proteins / genetics Drosophila Proteins / metabolism* Drosophila melanogaster / genetics Drosophila melanogaster / metabolism* Gene Expression Regulation Humans Intracellular Signaling Peptides and Proteins / genetics Intracellular Signaling Peptides and Proteins / metabolism* Larva / genetics Larva / metabolism* MAP Kinase Kinase 4 / genetics MAP Kinase Kinase 4 / metabolism* Mitogen-Activated Protein Kinases / genetics Mitogen-Activated Protein Kinases / metabolism Models, Biological Nuclear Proteins / genetics Nuclear Proteins / metabolism Protein Binding Protein Serine-Threonine Kinases / genetics Protein Serine-Threonine Kinases / metabolism* Signal Transduction* Trans-Activators / genetics Trans-Activators / metabolism Tumor Microenvironment YAP-Signaling Proteins src-Family Kinases / genetics src-Family Kinases / metabolism*
IF 7.497
引用数 52
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY
リソース情報
ショウジョウバエ 5993R-2 4005R-2