Please use this identifier to cite or link to this item:http://hdl.handle.net/20.500.12105/7870
Stabilization of p21 by mTORC1/4E-BP1 predicts clinical outcome of head and neck cancers
Nat Commun. 2016;7:10438.
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.
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