Show simple item record

dc.contributor.authorLLanos, Susana 
dc.contributor.authorGarcía-Pedrero, Juana M
dc.contributor.authorMorgado-Palacin, Lucia
dc.contributor.authorRodrigo, Juan P
dc.contributor.authorSerrano Marugan, Manuel
dc.identifier.citationNat Commun. 2016;7:10438.es_ES
dc.description.abstractThe levels, regulation and prognostic value of p21 in head and neck squamous cell carcinomas (HNSCC) has been puzzling for years. Here, we report a new mechanism of regulation of p21 by the mTORC1/4E-BP1 pathway. We find that non-phosphorylated 4E-BP1 interacts with p21 and induces its degradation. Accordingly, hyper-activation of mTORC1 results in phosphorylation of 4E-BP1 and stabilization of p21. In HNSCC, p21 levels strongly correlate with mTORC1 activity but not with p53 status. Finally, clinical data indicate that HNSCC patients with p21 and phospho-S6-double-positive tumours present a better disease-specific survival. We conclude that over-activation of the mTORC1/4E-BP1/p21 pathway is a frequent and clinically relevant alteration in HNSCC.es_ES
dc.description.sponsorshipWe are grateful to Reidar Grenman, Silvio Gutkind, Nahum Sonenberg, Gordon Peters, David Sabatini and Mariano Barbacid for sharing critical reagents. We also thank Aurora Astudillo, Aitana Vallina, Laura Alonso-Dura ́n and Eva Allonca for excellent technical assistance. Work in the laboratory of M.S. is funded by the CNIO and by grants from the Spanish Ministry of Economy (SAF) co-funded by the European Regional Development Fund, the European Research Council (ERC Advanced Grant), the Regional Government of Madrid co-funded by the European Social Fund, the Botin Foundation and BancoSantander (Santander Universities Global Division), the Ramon Areces Foundation an the AXA Foundation. Work in the laboratory of J.M.G.-P. and J.P.R. was supported bygrants from Plan Nacional de DþI 2013–2016 ISCIII (CP13/00013 andPI13/00259),RD12/0036/0015 of Red Tematica de Investigacio ́n Cooperativa en Cancer (RTICC), Spain and the FEDER Funding Program from the European Uniones_ES
dc.publisherNature Publishing Groupes_ES
dc.relation.isversionofPublisher's versiones_ES
dc.subject.meshAdaptor Proteins, Signal Transducinges_ES
dc.subject.meshAdult es_ES
dc.subject.meshAged es_ES
dc.subject.meshAged, 80 and over es_ES
dc.subject.meshCarcinoma, Squamous Cell es_ES
dc.subject.meshCell Line, Tumor es_ES
dc.subject.meshCyclin-Dependent Kinase Inhibitor p21 es_ES
dc.subject.meshFemale es_ES
dc.subject.meshGene Expression Regulation, Neoplastic es_ES
dc.subject.meshGenetic Predisposition to Disease es_ES
dc.subject.meshHead and Neck Neoplasms es_ES
dc.subject.meshHumans es_ES
dc.subject.meshMale es_ES
dc.subject.meshMechanistic Target of Rapamycin Complex 1 es_ES
dc.subject.meshMiddle Aged es_ES
dc.subject.meshMultiprotein Complexes es_ES
dc.subject.meshPhosphoproteins es_ES
dc.subject.meshTOR Serine-Threonine Kinases es_ES
dc.titleStabilization of p21 by mTORC1/4E-BP1 predicts clinical outcome of head and neck cancerses_ES
dc.rights.licenseAtribución-NoComercial-CompartirIgual 4.0 Internacional*
dc.contributor.funderEuropean Research Counciles_ES
dc.contributor.funderFundación Marcelo Botínes_ES
dc.contributor.funderFundación Ramón Areceses_ES
dc.contributor.funderAXA Research Fundationes_ES
dc.contributor.funderMinisterio de Economía y Competividad (España)es_ES
dc.identifier.journalNature communicationses_ES
dc.repisalud.orgCNIOCNIO::Grupos de investigación::Grupo de Supresión Tumorales_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/ PI13/00259es_ES

Files in this item

Acceso Abierto
Acceso Abierto

This item appears in the following Collection(s)

Show simple item record

Atribución-NoComercial-CompartirIgual 4.0 Internacional
This item is licensed under a: Atribución-NoComercial-CompartirIgual 4.0 Internacional