title: JAK/STAT signalling mediates cell survival in response to tissue stress.
abstract: Tissue homeostasis relies on the ability of tissues to respond to stress. Tissue regeneration and tumour models in Drosophila have shown that c-Jun amino-terminal kinase (JNK) acts as a prominent stress-response pathway promoting injury-induced apoptosis and compensatory proliferation. A central question remaining unanswered is how both responses are balanced by activation of a single pathway. Signalling through the Janus kinase/Signal transducers and activators of transcription (JAK/STAT) pathway, which is a potential JNK target, is implicated in promoting compensatory proliferation. While we observe JAK/STAT activation in imaginal discs upon damage, our data demonstrate that JAK/STAT and its downstream effector Zfh2 promote the survival of JNK signalling cells. The JNK component fos and the pro-apoptotic gene hid are regulated in a JAK/STAT-dependent manner. This molecular pathway restrains JNK-induced apoptosis and spatial propagation of JNK signalling, thereby limiting the extent of tissue damage, as well as facilitating systemic and proliferative responses to injury. We find that the pro-survival function of JAK/STAT also drives tumour growth under conditions of chronic stress. Our study defines the function of JAK/STAT in tissue stress and illustrates how crosstalk between conserved signalling pathways establishes an intricate equilibrium between proliferation, apoptosis and survival to restore tissue homeostasis.
authors.affiliation: Ludwig-Maximilians-University Munich, Faculty of Biology, Grosshaderner Strasse 2-4, Planegg-Martinsried 82152, Germany.
authors.forename: Marco
authors.initials: M
authors.lastname: La Fortezza
authors.affiliation: Ludwig-Maximilians-University Munich, Faculty of Biology, Grosshaderner Strasse 2-4, Planegg-Martinsried 82152, Germany.
authors.forename: Madlin
authors.initials: M
authors.lastname: Schenk
authors.affiliation: Ludwig-Maximilians-University Munich, Faculty of Biology, Grosshaderner Strasse 2-4, Planegg-Martinsried 82152, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Cosolo
authors.affiliation: Ludwig-Maximilians-University Munich, Faculty of Biology, Grosshaderner Strasse 2-4, Planegg-Martinsried 82152, Germany.
authors.forename: Addie
authors.initials: A
authors.lastname: Kolybaba
authors.affiliation: Ludwig-Maximilians-University Munich, Faculty of Biology, Grosshaderner Strasse 2-4, Planegg-Martinsried 82152, Germany.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Grass
authors.affiliation: Ludwig-Maximilians-University Munich, Faculty of Biology, Grosshaderner Strasse 2-4, Planegg-Martinsried 82152, Germany classen@bio.lmu.de.
authors.forename: Anne-Kathrin
authors.identifier: 0000-0001-5157-0749
authors.initials: AK
authors.lastname: Classen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D049109:Cell Proliferation / Q000235:genetics / Q000502:physiology; D002470:Cell Survival / Q000235:genetics / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004330:Drosophila / Q000378:metabolism* / Q000502:physiology; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation / Q000235:genetics / Q000502:physiology; D050791:STAT Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology
chemical_list: D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D008565:Membrane Proteins; D050791:STAT Transcription Factors; C464573:egr protein, Drosophila; C077729:Zfh2 protein, Drosophila; D048031:JNK Mitogen-Activated Protein Kinases
keywords: Cancer; Cell ablation; Cell survival; Compensatory proliferation; Eiger; Injury-induced apoptosis; JAK/STAT; JNK