Chronic activation of JNK JAK/STAT and oxidative stress signalling causes the loser cell status.,Nature Communications

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Chronic activation of JNK JAK/STAT and oxidative stress signalling causes the loser cell status.
Nature Communications ( IF 14.7 ) Pub Date : 2017-07-26 , DOI: 10.1038/s41467-017-00145-y
Iwo Kucinski _{1,

2} , Michael Dinan ₁ , Golnar Kolahgar ₁ , Eugenia Piddini _{1,

3}

Affiliation

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.

中文翻译：

JNK JAK/STAT 和氧化应激信号的慢性激活导致失败者细胞状态。

细胞竞争是细胞相互作用的一种形式，导致野生型 (WT) 细胞淘汰不太适合的细胞或失败者，从而影响整体组织健康。多种突变会导致细胞变得失败；然而，目前尚不清楚如何做到这一点。在这里，我们发现，携带功能无关的失败者突变（分钟和麻将）的果蝇翼盘细胞在细胞竞争之前表现出多种应激信号通路的共同激活，并发现这些途径共同解释了失败者状态。我们发现 JNK 信号传导抑制失败细胞的生长，而 JAK/STAT 信号传导促进竞争诱导的获胜细胞增殖。此外，我们发现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 过表达激活该途径就足以为 WT 邻居的细胞消除做好准备。由于氧化应激和 Nrf2 与多种疾病有关，因此细胞竞争可能在多种病理条件下发生。细胞竞争会导致不太适应的细胞（“失败者”）被淘汰，但为什么某些基因突变会使细胞变成失败者尚不清楚。在这里，作者表明，携带一些失败者突变的果蝇翼盘细胞会激活 Nrf2 和 JNK 信号传导，从而导致失败者状态。

更新日期：2017-07-26

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