دورية أكاديمية
Stabilization of p21 by mTORC1/4E-BP1 predicts clinical outcome of head and neck cancers
| العنوان: | Stabilization of p21 by mTORC1/4E-BP1 predicts clinical outcome of head and neck cancers |
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| المؤلفون: | LLanos, Susana, García-Pedrero, Juana M, Morgado-Palacin, Lucia, Rodrigo, Juan P, Serrano Marugan, Manuel |
| المساهمون: | Unión Europea. Comisión Europea. European Research Council (ERC), Botín Foundation, Fundación Ramón Areces, Fundación AXA, Ministerio de Economía y Competitividad (España) |
| بيانات النشر: | Nature Publishing Group |
| سنة النشر: | 2016 |
| المجموعة: | REPISALUD (REPositorio Institucional en SALUD del Instituto de Salud Carlos III - ISCIII) |
| مصطلحات موضوعية: | Adaptor Proteins, Signal Transducing, Adult, Aged, 80 and over, Carcinoma, Squamous Cell, Cell Line, Tumor, Cyclin-Dependent Kinase Inhibitor p21, Female, Gene Expression Regulation, Neoplastic, Genetic Predisposition to Disease, Head and Neck Neoplasms, Humans, Male, Mechanistic Target of Rapamycin Complex 1, Middle Aged, Multiprotein Complexes, Phosphoproteins, TOR Serine-Threonine Kinases |
| الوصف: | The 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. ; We 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 Union ; Sí |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 2041-1723 |
| العلاقة: | https://doi.org/10.1038/10.1038/ncomms10438Test.; info:eu-repo/grantAgreement/ES/CP13/00013; info:eu-repo/grantAgreement/ES/ PI13/00259; Nat Commun. 2016;7:10438.; http://hdl.handle.net/20.500.12105/7870Test; Nature communications |
| DOI: | 10.1038/ncomms10438 |
| الإتاحة: | https://doi.org/20.500.12105/7870Test https://doi.org/10.1038/ncomms10438Test https://doi.org/10.1038/10.1038/ncomms10438Test https://hdl.handle.net/20.500.12105/7870Test |
| حقوق: | http://creativecommons.org/licenses/by-nc-sa/4.0Test/ ; Atribución-NoComercial-CompartirIgual 4.0 Internacional ; open access |
| رقم الانضمام: | edsbas.4CCB1272 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 20411723 |
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| DOI: | 10.1038/ncomms10438 |