2. Academic Validation
  3. Stabilization of p21 by mTORC1/4E-BP1 predicts clinical outcome of head and neck cancers

Stabilization of p21 by mTORC1/4E-BP1 predicts clinical outcome of head and neck cancers

  • Nat Commun. 2016 Feb 2;7:10438. doi: 10.1038/ncomms10438.
Susana Llanos 1,  Juana M García-Pedrero 2,  Lucia Morgado-Palacin 1,  Juan P Rodrigo 2,  Manuel Serrano 1
Affiliations

Affiliations

  • 1 Tumor Suppression Group, Department of Molecular Oncology, Spanish National Cancer Research Centre (CNIO), 3 Melchor Fernandez Almagro Street, Madrid 28029, Spain.
  • 2 Department of Otolaryngology, Hospital Universitario Central de Asturias and Instituto Universitario de Oncología del Principado de Asturias, Universidad de Oviedo, Oviedo 33006, Spain.
PMID: 26832959 DOI: 10.1038/ncomms10438
Abstract

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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