Mechanical cell competition kills cells via induction of lethal p53 levels

Laura Wagstaff, Maja Goschorska, Kasia Kozyrska, Guillaume Duclos, Iwo Kucinski, Anatole Chessel, Lea A Hampton-O'Neil, Charles R Bradshaw, George E Allen, Emma L Rawlins, Pascal Silberzan, Rafael E Carazo Salas, Eugenia Piddini

Research output: Contribution to journalArticle (Academic Journal)peer-review

68 Citations (Scopus)
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Abstract

Cell competition is a quality control mechanism that eliminates unfit cells. How cells compete is poorly understood, but it is generally accepted that molecular exchange between cells signals elimination of unfit cells. Here we report an orthogonal mechanism of cell competition, whereby cells compete through mechanical insults. We show that MDCK cells silenced for the polarity gene scribble (scrib(KD)) are hypersensitive to compaction, that interaction with wild-type cells causes their compaction and that crowding is sufficient for scrib(KD) cell elimination. Importantly, we show that elevation of the tumour suppressor p53 is necessary and sufficient for crowding hypersensitivity. Compaction, via activation of Rho-associated kinase (ROCK) and the stress kinase p38, leads to further p53 elevation, causing cell death. Thus, in addition to molecules, cells use mechanical means to compete. Given the involvement of p53, compaction hypersensitivity may be widespread among damaged cells and offers an additional route to eliminate unfit cells.

Original languageEnglish
Article number11373
Number of pages14
JournalNature Communications
Volume7
DOIs
Publication statusPublished - 25 Apr 2016

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