Show simple item record

dc.contributor.authorde Carcer Diez, Guillermo 
dc.contributor.authorVenkateswaran, Sharavan Vishaan
dc.contributor.authorSalgueiro, Lorena
dc.contributor.authorEl Bakkali, Aicha
dc.contributor.authorSomogyi, Kalman
dc.contributor.authorRowald, Konstantina
dc.contributor.authorMontañés, Pablo
dc.contributor.authorSanclemente, Manuel
dc.contributor.authorEscobar, Beatriz 
dc.contributor.authorde Martino, Alba 
dc.contributor.authorMcGranahan, Nicholas
dc.contributor.authorMalumbres Martinez, Marcos 
dc.contributor.authorSotillo, Rocío
dc.date.accessioned2018-10-26T12:21:41Z
dc.date.available2018-10-26T12:21:41Z
dc.date.issued2018-08-01
dc.identifier.citationNat Commun. 2018; 9(1): 3012.es_ES
dc.identifier.issn2041-1723es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/6546
dc.description.abstractPolo-like kinase 1 (Plk1) is overexpressed in a wide spectrum of human tumors, being frequently considered as an oncogene and an attractive cancer target. However, its contribution to tumor development is unclear. Using a new inducible knock-in mouse model we report here that Plk1 overexpression results in abnormal chromosome segregation and cytokinesis, generating polyploid cells with reduced proliferative potential. Mechanistically, these cytokinesis defects correlate with defective loading of Cep55 and ESCRT complexes to the abscission bridge, in a Plk1 kinase-dependent manner. In vivo, Plk1 overexpression prevents the development of Kras-induced and Her2-induced mammary gland tumors, in the presence of increased rates of chromosome instability. In patients, Plk1 overexpression correlates with improved survival in specific breast cancer subtypes. Therefore, despite the therapeutic benefits of inhibiting Plk1 due to its essential role in tumor cell cycles, Plk1 overexpression has tumor-suppressive properties by perturbing mitotic progression and cytokinesis.es_ES
dc.description.sponsorshipWe are indebted to Stephen Taylor for the Sgo1 antibody. We thank Simone Kraut, Jessica Steiner, and the DKFZ light microscopy unit for excellent technical assistance. The results published here are in part based on data generated by TCGA pilot project (https://cancergenome.nih.gov/established by the NCI and the National Human Gen- ome Research Institute. The data were retrieved through dbGaP authorization (accession no. phs000178.v9.p8). S.V.V. was supported by the Marie Curie Network Ploidynet, funded by the European Union Seventh Framework Programme (FP7/2007–2013) under Grant Agreement #316964. L.S. is supported by a postdoctoral fellowship from Funda- cion Ramon Areces. Work in the R.S. laboratory was supported by an ERC starting grant (#281614), Marie Curie PCIG09-GA-2011 –293745 and the Howard Hughes Medical Institute. G.d.C. is funded by AECC Scientific Foundation (LABAE16017DECA). Work in the M.M. laboratory was supported by grants from the MINECO (SAF2015 –69920-R cofunded by ERDF-EU), Worldwide Cancer Research (WCR no. 150278), and Comunidad de Madrid (iLUNG-CM; B2017/BMD3884). The CNIO is a Severo Ochoa Center of Excellence (MINECO award SEV-2015-0510).es_ES
dc.language.isoenges_ES
dc.publisherNature Publishing Groupes_ES
dc.relation.isversionofPublisher's versiones_ES
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectPOLO-LIKE KINASEes_ES
dc.subjectBREAST-CANCERes_ES
dc.subjectTHERAPEUTIC TARGETSes_ES
dc.subjectANTICANCER THERAPYes_ES
dc.subjectMAMMALIAN-CELLSes_ES
dc.subjectESCRT MACHINERYes_ES
dc.subjectSCREENes_ES
dc.subjectANEUPLOIDYes_ES
dc.subjectEXPRESSIONes_ES
dc.subjectMICEes_ES
dc.titlePlk1 overexpression induces chromosomal instability and suppresses tumor developmentes_ES
dc.typeArtículoes_ES
dc.rights.licenseAtribución 4.0 Internacional*
dc.identifier.pubmedID30069007es_ES
dc.format.volume9es_ES
dc.format.number1es_ES
dc.format.page3012es_ES
dc.identifier.doi10.1038/s41467-018-05429-5es_ES
dc.contributor.funderFundación Ramón Areceses_ES
dc.contributor.funderEuropean Research Counciles_ES
dc.contributor.funderHoward Hughes Medical Institutees_ES
dc.contributor.funderFundación Científica AECCes_ES
dc.contributor.funderMinisterio de Economía y Competitividad (España)es_ES
dc.contributor.funderComunidad de Madrides_ES
dc.contributor.funderWorldwide Cancer Researches_ES
dc.description.peerreviewed
dc.identifier.e-issn2041-1723es_ES
dc.relation.publisherversionhttps:// doi.org/10.1038/s41467-018-05429-5es_ES
dc.identifier.journalNature communicationses_ES
dc.repisalud.institucionCNIOes_ES
dc.repisalud.orgCNIOCNIO::Grupos de investigaciónes_ES
dc.repisalud.orgCNIOCNIO::Grupos de investigación::Grupo de División Celular y Cánceres_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/SAF2015-69920-Res_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/EC/FP7/281614es_ES
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses_ES


Files in this item

Acceso Abierto
Thumbnail
Acceso Abierto
Thumbnail
Acceso Abierto
Thumbnail

This item appears in the following Collection(s)

Show simple item record

Atribución 4.0 Internacional
This item is licensed under a: Atribución 4.0 Internacional