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.

中文翻译：

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通过mTORC1 / 4E-BP1稳定p21可以预测头颈癌的临床结局。

头颈部鳞状细胞癌（HNSCC）中p21的水平，调控和预后价值一直令人困惑。在这里，我们报告了通过mTORC1 / 4E-BP1途径调控p21的新机制。我们发现，非磷酸化的4E-BP1与p21相互作用并诱导其降解。因此，mTORC1的过度激活导致4E-BP1的磷酸化和p21的稳定。在HNSCC中，p21水平与mTORC1活性密切相关，而与p53状态无关。最后，临床数据表明，患有p21和磷酸化S6双阳性肿瘤的HNSCC患者表现出更好的疾病特异性生存率。我们得出的结论是，mTORC1 / 4E-BP1 / p21途径的过度激活是HNSCC中常见且临床相关的改变。