Chronic activation of JNK JAK/STAT and oxidative stress signalling causes the loser cell status.
Chronic activation of JNK JAK/STAT and oxidative stress signalling causes the loser cell status.
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DOI：
10.1038/s41467-017-00145-y
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发表时间：
2017-07-26
影响因子：
16.6
通讯作者：
Piddini E
中科院分区：
文献类型：
--
作者：
Kucinski I;Dinan M;Kolahgar G;Piddini E
细胞竞争是一种细胞相互作用的形式，导致野生型(WT)细胞消除不太适合的细胞或失败者，影响整体组织健康。几种突变可以导致细胞成为失败者；然而，目前还不清楚是如何发生的。在这里，我们显示了携带功能无关的失败者突变(分钟和麻将)的果蝇翅膀盘细胞在细胞竞争之前表现出多个应激信号通路的共同激活，并发现这些通路共同解释了失败者状态。我们发现JNK信号抑制失败者的生长，而JAK/STAT信号促进竞争诱导的胜利者细胞增殖。此外，我们还表明，失败者表现出氧化应激反应激活，并且引人注目的是，仅通过Nrf2过表达激活这一途径，就足以启动细胞，使其被WT邻居消除。由于氧化应激和Nrf2与几种疾病有关，细胞竞争可能在许多病理条件下发生。细胞竞争会导致不太适合的细胞(失败者)被移除，但为什么一些基因突变会让细胞变成失败者，这一点尚不清楚。在这里，作者表明，携带一些失败者突变的果蝇翅膀盘细胞激活了Nrf2和JNK信号，这有助于失败者状态。
Cell competition is a form of cell interaction that causes the elimination of less fit cells, or losers, by wild-type (WT) cells, influencing overall tissue health. Several mutations can cause cells to become losers; however, it is not known how. Here we show that Drosophila wing disc cells carrying functionally unrelated loser mutations (Minute and mahjong) display the common activation of multiple stress signalling pathways before cell competition and find that these pathways collectively account for the loser status. We find that JNK signalling inhibits the growth of losers, while JAK/STAT signalling promotes competition-induced winner cell proliferation. Furthermore, we show that losers display oxidative stress response activation and, strikingly, that activation of this pathway alone, by Nrf2 overexpression, is sufficient to prime cells for their elimination by WT neighbours. Since oxidative stress and Nrf2 are linked to several diseases, cell competition may occur in a number of pathological conditions. Cell competition causes the removal of less fit cells (‘losers’) but why some gene mutations turn cells into losers is unclear. Here, the authors show that Drosophila wing disc cells carrying some loser mutations activate Nrf2 and JNK signalling, which contribute to the loser status.
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作者：
Bunker BD;Nellimoottil TT;Boileau RM;Classen AK;Bilder D
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