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.
Keywords: Cancer; Cell ablation; Cell survival; Compensatory proliferation; Eiger; Injury-induced apoptosis; JAK/STAT; JNK.
© 2016. Published by The Company of Biologists Ltd.