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


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.

SUBMITTER: Llanos S 

PROVIDER: S-EPMC4740818 | biostudies-other | 2016

REPOSITORIES: biostudies-other

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

Llanos Susana S   García-Pedrero Juana M JM   Morgado-Palacin Lucia L   Rodrigo Juan P JP   Serrano Manuel M  

Nature communications 20160202


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, cl  ...[more]

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