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Mechanical cell competition kills cells via induction of lethal p53 levels.

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Wagstaff, Laura 
Goschorska, Maja 
Kozyrska, Kasia 
Duclos, Guillaume 
Kucinski, Iwo 


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.



Animals, Apoptosis, Biomechanical Phenomena, Cell Communication, Dogs, Drosophila, Drosophila Proteins, Madin Darby Canine Kidney Cells, Membrane Proteins, Tumor Suppressor Protein p53, rho-Associated Kinases

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Nat Commun

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Springer Science and Business Media LLC
Medical Research Council (G0900424)
Wellcome Trust (105602/Z/14/Z)
Biotechnology and Biological Sciences Research Council (BB/K006320/1)
Wellcome Trust (092096/Z/10/Z)
European Research Council (243283)
Cancer Research Uk (None)
This work was supported by a Cancer Research UK Programme Grant (EP and LW A12460), a Royal Society University Research fellowship to EP (UF0905080), a Wellcome Trust PhD studentship to I.K, a Cambridge Cancer Centre PhD studentship to MG and Core grant funding from the Wellcome Trust (092096) and CRUK (C6946/A14492).