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Centrosome amplification arises before neoplasia and increases upon p53 loss in tumorigenesis

2018-05Journal article Open access
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dc.contributor.authorLopes, Carla A.M.
dc.contributor.authorMesquita, Marta
dc.contributor.authorCunha, Ana Isabel
dc.contributor.authorCardoso, Joana
dc.contributor.authorCarapeta, Sara
dc.contributor.authorLaranjeira, Cátia
dc.contributor.authorPinto, António E.
dc.contributor.authorPereira-Leal, José B.
dc.contributor.authorDias-Pereira, António
dc.contributor.authorBettencourt-Dias, Mónica
dc.contributor.authorChaves, Paula
dc.date.accessioned2018-05-15T12:02:45Z
dc.date.available2018-12-01T01:30:09Z
dc.date.issued2018-05
dc.descriptionThe uploaded article version is the Epub Ahead of Print version of the article, posted online 8 May 2018. It has been submitted to peer-review.pt_PT
dc.descriptionThe deposited article version contains attached the supplementary materials within the pdf.pt_PT
dc.description.abstractCentrosome abnormalities are a typical hallmark of human cancers. However, the origin and dynamics of such abnormalities in human cancer are not known. In this study, we examined centrosomes in Barrett's esophagus tumorigenesis, a well-characterized multistep pathway of progression, from the premalignant condition to the metastatic disease. This human cancer model allows the study of sequential steps of progression within the same patient and has representative cell lines from all stages of disease. Remarkably, centrosome amplification was detected as early as the premalignant condition and was significantly expanded in dysplasia. It was then present throughout malignant transformation both in adenocarcinoma and metastasis. The early expansion of centrosome amplification correlated with and was dependent on loss of function of the tumor suppressor p53 both through loss of wild-type expression and hotspot mutations. Our work shows that centrosome amplification in human tumorigenesis can occur before transformation, being repressed by p53. These findings suggest centrosome amplification in humans can contribute to tumor initiation and progression.pt_PT
dc.description.sponsorshipFundação para a Ciência e a Tecnologia–Harvard Medical School Program Portugal grant: (HMSP-CT/SAU-ICT/0075/2009); Liga Portuguesa Contra o Cancro; European Molecular Biology Organization Installation; Sociedade Portuguesa de Gastroenterologia.pt_PT
dc.description.versionN/Apt_PT
dc.identifier.citationCarla A.M. Lopes, Marta Mesquita, Ana Isabel Cunha, Joana Cardoso, Sara Carapeta, Cátia Laranjeira, António E. Pinto, José B. Pereira-Leal, António Dias-Pereira, Mónica Bettencourt-Dias, Paula Chaves (2018). Centrosome amplification arises before neoplasia and increases upon p53 loss in tumorigenesis.J Cell Biol May 2018, jcb.201711191; DOI: 10.1083/jcb.201711191pt_PT
dc.identifier.doi10.1083/jcb.201711191pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.7/867
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherRockefeller University Presspt_PT
dc.relation.publisherversionhttp://jcb.rupress.org/content/early/2018/05/07/jcb.201711191.longpt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectCancerpt_PT
dc.subjecthuman cancerpt_PT
dc.subjectOrganellespt_PT
dc.subjectCentrosome amplificationpt_PT
dc.subjectp53pt_PT
dc.titleCentrosome amplification arises before neoplasia and increases upon p53 loss in tumorigenesispt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/HMSP-CT%2FSAU-ICT%2F0075%2F2009/PT
oaire.citation.endPage11pt_PT
oaire.citation.startPage1pt_PT
oaire.citation.titleJournal of Cell Biologypt_PT
oaire.citation.volume[Epub ahead of print]pt_PT
oaire.fundingStream3599-PPCDT
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isProjectOfPublication950d9933-b1f8-43c9-834b-36eda23788ff
relation.isProjectOfPublication.latestForDiscovery950d9933-b1f8-43c9-834b-36eda23788ff

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