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Over-elongation of centrioles in cancer promotes centriole amplification and chromosome missegregation

2018-03-28Journal article Open access
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dc.contributor.authorMarteil, Gaëlle
dc.contributor.authorGuerrero, Adan
dc.contributor.authorVieira, André F
dc.contributor.authorde Almeida, Bernardo P
dc.contributor.authorMachado, Pedro
dc.contributor.authorMendonça, Susana
dc.contributor.authorMesquita, Marta
dc.contributor.authorVillarreal, Beth
dc.contributor.authorFonseca, Irina
dc.contributor.authorFrancia, Maria E
dc.contributor.authorDores, Katharina
dc.contributor.authorMartins, Nuno P
dc.contributor.authorJana, Swadhin C
dc.contributor.authorTranfield, Erin M
dc.contributor.authorBarbosa-Morais, Nuno L
dc.contributor.authorParedes, Joana
dc.contributor.authorPellman, David
dc.contributor.authorGodinho, Susana A
dc.contributor.authorBettencourt-Dias, Mónica
dc.date.accessioned2018-04-02T11:42:29Z
dc.date.available2018-04-02T11:42:29Z
dc.date.issued2018-03-28
dc.descriptionThis deposit is composed by the main article plus the supplementary materials of the publication.pt_PT
dc.description.abstractCentrosomes are the major microtubule organising centres of animal cells. Deregulation in their number occurs in cancer and was shown to trigger tumorigenesis in mice. However, the incidence, consequence and origins of this abnormality are poorly understood. Here, we screened the NCI-60 panel of human cancer cell lines to systematically analyse centriole number and structure. Our screen shows that centriole amplification is widespread in cancer cell lines and highly prevalent in aggressive breast carcinomas. Moreover, we identify another recurrent feature of cancer cells: centriole size deregulation. Further experiments demonstrate that severe centriole over-elongation can promote amplification through both centriole fragmentation and ectopic procentriole formation. Furthermore, we show that overly long centrioles form over-active centrosomes that nucleate more microtubules, a known cause of invasiveness, and perturb chromosome segregation. Our screen establishes centriole amplification and size deregulation as recurrent features of cancer cells and identifies novel causes and consequences of those abnormalities.pt_PT
dc.description.sponsorshipFCT- Harvard Medical School Program Portugal grant: (HMSP-CT/SAU-ICT/0075/2009); Fundação para a Ciência e a Tecnologia grants: (SFRH/BPD/98439/2013, SFRH/BPD/82420/2011, POCI-01-0145-FEDER-016390, PTDC/BIM-ONC/6858/2014); EMBO installation grant; ERC grant: (ERC-2010-StG-261344).pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationMarteil, G., Guerrero, A., Vieira, A. F., de Almeida, B. P., Machado, P., Mendonça, S., Mesquita, M., Villarreal, B., Fonseca, I., Francia, M. E., Dores, K., Martins, N. P., Jana, S. C., Tranfield, E. M., Barbosa-Morais, N. L., Paredes, J., Pellman, D., Godinho, S. A., Bettencourt-Dias, M. (2018). Over-elongation of centrioles in cancer promotes centriole amplification and chromosome missegregation. Nature Communications, 9(1):1258. doi:10.1038/s41467-018-03641-xpt_PT
dc.identifier.doi10.1038/s41467-018-03641-xpt_PT
dc.identifier.urihttp://hdl.handle.net/10400.7/857
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherNature Publishing Grouppt_PT
dc.relationPOCI-01-0145-FEDER-016390pt_PT
dc.relationCAUSES AND CONSEQUENCES OF CENTROSOME CHANGES IN CANCER
dc.relationMOLECULAR CIRCUITS CONTROLLING CENTRIOLE NUMBER IN SPACE AND TIME
dc.relationControl of Centriole Structure And Number
dc.relation"Length matters: Causes and consequences of centriole length deregulation in cancer"
dc.relation.publisherversionhttps://www.nature.com/articles/s41467-018-03641-xpt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectCancerpt_PT
dc.subjectCentrosomespt_PT
dc.subjectCentriolespt_PT
dc.subjectChromosomespt_PT
dc.titleOver-elongation of centrioles in cancer promotes centriole amplification and chromosome missegregationpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleCAUSES AND CONSEQUENCES OF CENTROSOME CHANGES IN CANCER
oaire.awardTitleMOLECULAR CIRCUITS CONTROLLING CENTRIOLE NUMBER IN SPACE AND TIME
oaire.awardTitleControl of Centriole Structure And Number
oaire.awardTitle"Length matters: Causes and consequences of centriole length deregulation in cancer"
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/HMSP-CT%2FSAU-ICT%2F0075%2F2009/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//SFRH%2FBPD%2F98439%2F2013/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//SFRH%2FBPD%2F82420%2F2011/PT
oaire.awardURIinfo:eu-repo/grantAgreement/EC/FP7/261344/EU
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FBIM-ONC%2F6858%2F2014/PT
oaire.citation.endPage17pt_PT
oaire.citation.issue1pt_PT
oaire.citation.startPage1pt_PT
oaire.citation.titleNature Communicationspt_PT
oaire.citation.volume9pt_PT
oaire.fundingStream3599-PPCDT
oaire.fundingStreamFP7
oaire.fundingStream3599-PPCDT
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100008530
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameEuropean Commission
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isProjectOfPublication950d9933-b1f8-43c9-834b-36eda23788ff
relation.isProjectOfPublicatione85512e3-4f80-40ff-acd9-63182cef602d
relation.isProjectOfPublication08fa3ddb-f995-40a0-96f9-044e8ad68e4e
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relation.isProjectOfPublication8282ac35-73a1-4f8e-95da-dbed8651602e
relation.isProjectOfPublication.latestForDiscoverye85512e3-4f80-40ff-acd9-63182cef602d

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