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

Susana Llanos (), Juana M. García-Pedrero, Lucia Morgado-Palacin, Juan P. Rodrigo and Manuel Serrano ()
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Susana Llanos: Tumor Suppression Group, Spanish National Cancer Research Centre (CNIO)
Juana M. García-Pedrero: Hospital Universitario Central de Asturias and Instituto Universitario de Oncología del Principado de Asturias, Universidad de Oviedo
Lucia Morgado-Palacin: Tumor Suppression Group, Spanish National Cancer Research Centre (CNIO)
Juan P. Rodrigo: Hospital Universitario Central de Asturias and Instituto Universitario de Oncología del Principado de Asturias, Universidad de Oviedo
Manuel Serrano: Tumor Suppression Group, Spanish National Cancer Research Centre (CNIO)

Nature Communications, 2016, vol. 7, issue 1, 1-11

Abstract: 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.

Date: 2016
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DOI: 10.1038/ncomms10438

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