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

Iwo Kucinski, Michael Dinan, Golnar Kolahgar and Eugenia Piddini ()
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Iwo Kucinski: University of Cambridge
Michael Dinan: University of Cambridge
Golnar Kolahgar: University of Cambridge
Eugenia Piddini: University of Cambridge

Nature Communications, 2017, vol. 8, issue 1, 1-13

Abstract: Abstract 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.

Date: 2017
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DOI: 10.1038/s41467-017-00145-y

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