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dc.contributor.authorFernández, Rosa M. H.
dc.contributor.authorRuiz Miró, Maria
dc.contributor.authorDolcet Roca, Xavier
dc.contributor.authorAldea, Martí
dc.contributor.authorGarí Marsol, Eloi
dc.date.accessioned2017-01-24T13:21:40Z
dc.date.issued2011
dc.identifier.issn0950-9232
dc.identifier.urihttp://hdl.handle.net/10459.1/59092
dc.description.abstractAlterations in the levels of adhesion and motility of cells are critical events in the development of metastasis. Cyclin D1 (CycD1) is one of the most frequently amplified oncogenes in many types of cancers and it is also associated with the development of metastasis. Despite this, we still do not know which are all the relevant pathways by which CycD1 induces oncogenic processes. CycD1 functions can be either dependent or independent of the cyclin-dependent kinase Cdk4, and they affect several cellular aspects such as proliferation, cell attachment and migration. In this work, we reveal a novel function of CycD1 that fosters our understanding of the oncogenic potential of CycD1. We show that CycD1 binds to the small GTPases Ral A and B, which are involved, through exocyst regulation, in the progression of metastatic cancers, inducing anchorage-independent growth and cell survival of transformed cells. We show that CycD1 binds active Ral complexes and the exocyst protein Sec6, and co-localizes with Ral GTPases in trans-Golgi and exocyst-rich regions. We have also observed that CycD1–Cdk4 phosphorylates the Ral GEF Rgl2 ‘in vitro’ and that CycD1–Cdk4 activity stimulates accumulation of the Ral GTP active forms. In accordance with this, our data suggest that CycD1–Cdk4 enhances cell detachment and motility in collaboration with Ral GTPases. This new function may help explain the contribution of CycD1 to tumor spreading.ca_ES
dc.description.sponsorshipWe thank N Agell, C Yeaman, JL Bos, M Matsuda, X Bustelo, P Crespo, MA del Pozo and J Herreros for the gift of plasmids and reagents, and also N Eritja,MBozic, JM Valdivielso, Lluı´s Fajas, Eloi Montanez and SaraWickstro¨m for technical advice. We are grateful to J Odajima and P Sicinski for providing CCND1 / and CCND1þ/þ immortalized MEFs, andMHendrix and E Seftor for providing R3327-50A cells. We thank S Rius, I Navarro, I Montoliu and MA Cornado´ for their technical assistance and the members of CYC lab for helpful discussions. This work was funded by the Ministry of Education and Science of Spain BFU2007-65640/BMC (Eloi Garı´) and BFU2007- 67929-C02-01 (Martı´ Aldea) and Consolider-Ingenio 2010 (CSD2007-00015). RMH Ferna´ ndez and M Ruiz-Miró were supported by predoctoral fellowships from the Ministry of Education and Science of Spain.ca_ES
dc.language.isoengca_ES
dc.publisherNatureca_ES
dc.relationMIECI/PN2004-2007/ BFU2007-65640ca_ES
dc.relationMIECI/PN2004-2007/ BFU2007-67929-C02-01ca_ES
dc.relation.isformatofReproducció del document publicat a https://doi.org/10.1038/onc.2010.577ca_ES
dc.relation.ispartofOncogene, 2011, vol. 30, p. 1936-1946ca_ES
dc.rights(c) Macmillan Publishers Limited, 2011ca_ES
dc.subjectCyclin D1ca_ES
dc.subjectRal GTPasesca_ES
dc.subjectExocystca_ES
dc.subjectCell motility cell adhesionca_ES
dc.subjectTumor spreadingca_ES
dc.titleCyclin D1 interacts and collaborates with Ral GTPases enhancing cell detachment and motilityca_ES
dc.typearticleca_ES
dc.identifier.idgrec016534
dc.type.versionpublishedVersionca_ES
dc.rights.accessRightsinfo:eu-repo/semantics/restrictedAccessca_ES
dc.identifier.doihttps://doi.org/10.1038/onc.2010.577
dc.date.embargoEndDate2025-01-01


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