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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
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*
Substances
-
Actins
-
Drosophila Proteins
-
Intracellular Signaling Peptides and Proteins
-
Nuclear Proteins
-
Trans-Activators
-
YAP-Signaling Proteins
-
Yki protein, Drosophila
-
src-Family Kinases
-
Protein Serine-Threonine Kinases
-
hpo protein, Drosophila
-
Mitogen-Activated Protein Kinases
-
MAP Kinase Kinase 4