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

2018-03Journal article Open Access
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dc.contributor.authorMarteil, Gaelle
dc.contributor.authorGuerrero, Adan
dc.contributor.authorVieira, Andre F.
dc.contributor.authorde Almeida, Bernardo P.
dc.contributor.authorMachado, Pedro
dc.contributor.authorMendonca, 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, Monica
dc.date.accessioned2018-12-07T14:53:36Z
dc.date.available2018-12-07T14:53:36Z
dc.date.issued2018-03
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.
dc.description.sponsorshipFCT [SFRH/BPD/98439/2013, SFRH/BPD/82420/2011, POCI-01-0145-FEDER-016390, PTDC/BIM-ONC/6858/2014]; IGC, an EMBO installation grant; ERC [ERC-2010-StG-261344]; FCT-Harvard Medical School Program Portugal grant [HMSP-CT/SAU-ICT/0075/2009]
dc.description.versioninfo:eu-repo/semantics/publishedVersion
dc.identifier.doi10.1038/s41467-018-03641-x
dc.identifier.issn2041-1723
dc.identifier.urihttp://hdl.handle.net/10400.1/11598
dc.language.isoeng
dc.peerreviewedyes
dc.publisherNature Publishing Group
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.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectHamster ovary cells
dc.subjectHuman breast-tumors
dc.subjectCentrosome amplification
dc.subjectKinase 4
dc.subjectPericentriolar material
dc.subjectExpression profiles
dc.subjectMolecular subtypes
dc.subjectColorectal-cancer
dc.subjectExtra centrosomes
dc.subjectDna-damage
dc.titleOver-elongation of centrioles in cancer promotes centriole amplification and chromosome missegregation
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.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/FCT/3599-PPCDT/HMSP-CT%2FSAU-ICT%2F0075%2F2009/PT
oaire.awardURIinfo:eu-repo/grantAgreement/EC/FP7/261344/EU
oaire.citation.startPage1258
oaire.citation.titleNature Communications
oaire.citation.volume9
oaire.fundingStream3599-PPCDT
oaire.fundingStreamFP7
person.familyNameAlmeida
person.givenNameBernardo
person.identifier.orcid0000-0002-6084-6775
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.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
rcaap.rightsopenAccess
rcaap.typearticle
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relation.isAuthorOfPublication.latestForDiscoverya20b550d-d54a-46ae-9e17-3eb5fa5409cc
relation.isProjectOfPublication669231a3-17dc-4092-8d05-f31ebf88cace
relation.isProjectOfPublicationc1f73e86-0df5-4afc-99b2-01b1aad19d4c
relation.isProjectOfPublicationc216892a-662a-4aff-bf64-b6d059d05469
relation.isProjectOfPublication27a623de-1694-4dc5-baef-fa264cc56e2f
relation.isProjectOfPublication.latestForDiscovery27a623de-1694-4dc5-baef-fa264cc56e2f

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