Por favor, use este identificador para citar o enlazar este Item:http://hdl.handle.net/20.500.12105/7870
Título
Stabilization of p21 by mTORC1/4E-BP1 predicts clinical outcome of head and neck cancers
Autor(es)
Fecha de publicación
2016-02-02
Cita
Nat Commun. 2016;7:10438.
Idioma
Inglés
Tipo de documento
journal article
Resumen
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.
MESH
Adaptor Proteins, Signal Transducing | Adult | Aged | 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
Versión en línea
DOI
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