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dc.contributor.authorWagstaff, Lauraen
dc.contributor.authorGoschorska, Majaen
dc.contributor.authorKozyrska, Kasiaen
dc.contributor.authorDuclos, Guillaumeen
dc.contributor.authorKucinski, Iwoen
dc.contributor.authorChessel, Anatoleen
dc.contributor.authorHampton-O’Neil, Leaen
dc.contributor.authorBradshaw, Charlesen
dc.contributor.authorAllen, George Een
dc.contributor.authorRawlins, Emmaen
dc.contributor.authorSilberzan, Pascalen
dc.contributor.authorCarazo, Salas Rafael Een
dc.contributor.authorPiddini, Eugeniaen
dc.date.accessioned2016-03-31T15:30:33Z
dc.date.available2016-03-31T15:30:33Z
dc.date.issued2016-04-25en
dc.identifier.issn2041-1723
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/254751
dc.description.abstractCell 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 (scribKD) are hypersensitive to compaction, that interaction with wild-type cells causes their compaction and that crowding is sufficient for scribKD 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.
dc.description.sponsorshipThis 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).
dc.languageEnglishen
dc.language.isoenen
dc.publisherNature Publishing Group
dc.rightsAttribution 4.0 International
dc.rightsAttribution 4.0 Internationalen
dc.rightsAttribution 4.0 Internationalen
dc.rightsAttribution 4.0 Internationalen
dc.rightsAttribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectmechanical cell competitionen
dc.subjectcell deathen
dc.subjectmechanical stressen
dc.subjectcell densityen
dc.subjectcell crowdingen
dc.subjectp53en
dc.subjectp38en
dc.subjectROCKen
dc.subjectscribbleen
dc.subjectmigrationen
dc.titleMechanical cell competition kills cells via induction of lethal p53 levelsen
dc.typeArticle
dc.description.versionThis is the final version of the article. It first appeared from Nature Publishing Group via https://doi.org/10.1038/ncomms11373en
prism.number11373en
prism.publicationDate2016en
prism.publicationNameNature Communicationsen
prism.volume7en
dc.rioxxterms.funderCRUK
dc.rioxxterms.funderWellcome Trust
dc.rioxxterms.projectidA12460
dc.rioxxterms.projectidC6946/A14492
dc.rioxxterms.projectid092096
dcterms.dateAccepted2016-03-18en
rioxxterms.versionofrecord10.1038/ncomms11373en
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/en
rioxxterms.licenseref.startdate2016-04-25en
dc.contributor.orcidKucinski, Iwo [0000-0002-9385-0359]
dc.contributor.orcidBradshaw, Charles [0000-0002-3528-458X]
dc.contributor.orcidRawlins, Emma [0000-0001-7426-3792]
dc.contributor.orcidPiddini, Eugenia [0000-0003-3901-076X]
dc.identifier.eissn2041-1723
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idMRC (G0900424)
pubs.funder-project-idWELLCOME TRUST (105602/Z/14/Z)
pubs.funder-project-idBBSRC (BB/K006320/1)
pubs.funder-project-idWellcome Trust (092096/Z/10/Z)
pubs.funder-project-idEuropean Research Council (243283)
pubs.funder-project-idCancer Research UK (A14492)
cam.orpheus.successThu Jan 30 12:54:35 GMT 2020 - The item has an open VoR version.*
rioxxterms.freetoread.startdate2100-01-01


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International