Chronic activation of JNK JAK/STAT and oxidative stress signalling causes the loser cell status
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Kucinski, I., Dinan, M., Kolahgar, G., & Piddini, E. (2017). Chronic activation of JNK JAK/STAT and oxidative stress signalling causes the loser cell status. Nature Communications, 8 (1. 136)https://doi.org/10.1038/s41467-017-00145-y
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.
This work was supported by a Cancer Research UK Programme Grant (A12460) and a Royal Society University Research fellowship to E.P. (UF0905080), a Wellcome Trust PhD studentship to I.K., a Wellcome Trust PhD studentship to M.D. and Core grant funding from the Wellcome Trust (092096) and CRUK (C6946/A14492).
Wellcome Trust (092096/Z/10/Z)
Cancer Research UK (A14492)
External DOI: https://doi.org/10.1038/s41467-017-00145-y
This record's URL: https://www.repository.cam.ac.uk/handle/1810/266757