Journal
NATURE COMMUNICATIONS
Volume 7, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms10438
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Funding
- CNIO
- Spanish Ministry of Economy (SAF)
- European Regional Development Fund
- European Research Council (ERC Advanced Grant)
- Regional Government of Madrid
- European Social Fund
- Botin Foundation
- Banco Santander (Santander Universities Global Division)
- Ramon Areces Foundation
- AXA Foundation
- Plan Nacional de I+D+I ISCIII of Red Tematica de Investigacion Cooperativa en Cancer (RTICC), Spain [CP13/00013, PI13/00259]
- FEDER Funding Program from the European Union
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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.
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