Loss of Rab5 drives non-autonomous cell proliferation through TNF and Ras signaling in Drosophila
Copyright policy )Loss of Rab5 drives non-autonomous cell proliferation through TNF and Ras signaling in Drosophila
Deregulation of the endocytic machinery has been implicated in human cancers. However, the mechanism by which endocytic defects drive cancer development remains to be clarified. Here, we find through a genetic screen in Drosophila that loss of Rab5, a protein required for early endocytic trafficking, drives non-autonomous cell proliferation in imaginal epithelium. Our genetic data indicate that dysfunction of Rab5 leads to cell-autonomous accumulation of Eiger (a TNF homolog) and EGF receptor (EGFR), which causes activation of downstream JNK and Ras signaling, respectively. JNK signaling and its downstream component Cdc42 cooperate with Ras signaling to induce upregulation of a secreted growth factor Upd (an IL-6 homolog) through inactivation of the Hippo pathway. Such non-autonomous tissue growth triggered by Rab5 defect could contribute to epithelial homeostasis as well as cancer development within heterogeneous tumor microenvironment.
- Kyoto University Japan
- National Presto Industries United States
- Kobe University Japan
- Japan Science and Technology Agency Japan
Green Fluorescent Proteins, Protein Serine-Threonine Kinases, Eye, Tissue growth regulation, Models, Biological, Animals, Genetically Modified, Rab5, GTP-Binding Proteins, Animals, Drosophila Proteins, Humans, Molecular Biology, Cell Proliferation, Microscopy, Confocal, Models, Genetic, Intracellular Signaling Peptides and Proteins, JNK Mitogen-Activated Protein Kinases, Membrane Proteins, Cell Biology, ErbB Receptors, Drosophila melanogaster, Imaginal Discs, Tumorigenesis, Mutation, Drosophila, RNA Interference, Cell–cell interaction, Developmental Biology
Green Fluorescent Proteins, Protein Serine-Threonine Kinases, Eye, Tissue growth regulation, Models, Biological, Animals, Genetically Modified, Rab5, GTP-Binding Proteins, Animals, Drosophila Proteins, Humans, Molecular Biology, Cell Proliferation, Microscopy, Confocal, Models, Genetic, Intracellular Signaling Peptides and Proteins, JNK Mitogen-Activated Protein Kinases, Membrane Proteins, Cell Biology, ErbB Receptors, Drosophila melanogaster, Imaginal Discs, Tumorigenesis, Mutation, Drosophila, RNA Interference, Cell–cell interaction, Developmental Biology
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