Stabilization of p21 by mTORC1/4E-BP1 predicts clinical outcome of head and neck cancers.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 26832959.
- Also identified by DOI 10.1038/ncomms10438 and PMC identifier 4740818.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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.
Medical subject headings
- Adaptor Proteins, Signal Transducing
- Carcinoma, Squamous Cell
- Cyclin-Dependent Kinase Inhibitor p21
- Head and Neck Neoplasms
- Multiprotein Complexes
- Phosphoproteins
- TOR Serine-Threonine Kinases