JAK/STAT signalling mediates cell survival in response to tissue stress
JAK/STAT signalling mediates cell survival in response to tissue stress
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DOI：
10.1242/dev.132340
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发表时间：
2016-08-15
期刊：
影响因子：
4.6
通讯作者：
Classen, Anne-Kathrin
中科院分区：
文献类型：
--
作者：
La Fortezza, Marco;Schenk, Madlin;Classen, Anne-Kathrin
组织稳态依赖于组织对压力做出反应的能力。果蝇的组织再生和肿瘤模型表明，c-Jun氨基末端激酶（JNK）作为一个突出的应激反应途径，促进损伤诱导的细胞凋亡和代偿性增殖。一个尚未回答的中心问题是，这两种反应如何通过激活单一途径来平衡。通过Janus激酶/信号转导和转录激活因子（JAK/STAT）途径的信号传导（其是潜在的JNK靶点）涉及促进代偿性增殖。虽然我们观察到JAK/STAT激活的成虫盘损伤后，我们的数据表明，JAK/STAT和其下游效应Zfh 2促进JNK信号细胞的存活。JNK组分fos和促凋亡基因hid以JAK/STAT依赖性方式调节。该分子途径抑制JNK诱导的细胞凋亡和JNK信号传导的空间传播，从而限制组织损伤的程度，以及促进对损伤的全身性和增殖性反应。我们发现JAK/STAT的促生存功能也在慢性应激条件下驱动肿瘤生长。我们的研究定义了JAK/STAT在组织应激中的功能，并说明了保守信号通路之间的串扰如何在增殖、凋亡和存活之间建立复杂的平衡，以恢复组织稳态。
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.