CLIN CANCER RES：Notch信号功能丧失促进头颈部癌发生

2018-12-22 MedSci MedSci原创

头颈部鳞状细胞癌（HNSCC）是世界范围内常见的癌症，其发病与烟草使用，大量酒精摄入和高危人乳头瘤病毒（HPV）有关。Notch信号通路与细胞分化有关，涉及不同的下游靶标，根据组织类型及分期产生不同影响。NOTCH1是HPV阳性和HPV阴性头颈部鳞状细胞癌中最常见的突变基因之一。有研究认为这些突变会使Notch的功能失活，其他研究则有相反看法，认为在头颈部鳞状细胞癌中Notch信号传导增加。CLI

头颈部鳞状细胞癌（HNSCC）是世界范围内常见的癌症，其发病与烟草使用，大量酒精摄入和高危人乳头瘤病毒（HPV）有关。Notch信号通路与细胞分化有关，涉及不同的下游靶标，根据组织类型及分期产生不同影响。NOTCH1是HPV阳性和HPV阴性头颈部鳞状细胞癌中最常见的突变基因之一。有研究认为这些突变会使Notch的功能失活，其他研究则有相反看法，认为在头颈部鳞状细胞癌中Notch信号传导增加。CLIN CANCER RES近期发表了一篇文章，进一步明确这一问题。

作者利用基因工程小鼠（GEM）模型评估Notch信号在HPV阳性和HPV阴性头颈部鳞状细胞癌中的作用，模型中表达HPV16 E6和E7癌蛋白或获得功能的p53突变体，并且通过表达失活形式的MAML1（DNMAML1）（Notch信号传导的所需转录共激活因子）来灭活经典Notch信号传导。研究结果表明，经典Notch信号传导的丧失增加了肿瘤发生，并且还导致核β-连环蛋白的增加，核β-连环蛋白是致瘤潜力的标志物。其与经典Notch信号传导丧失相结合时，HPV癌基因导致癌症总体发病率最高，并且分化程度差的癌症数量最多。

文章最后认为，这些研究结果明确了经典Notch信号丢失对头颈癌发生的影响。

原始出处：

Patrick E. Nyman, Darya Buehler, et al. Loss of Function of Canonical Notch Signaling Drives Head and Neck Carcinogenesis. CLIN CANCER RES. December 2018 doi: 10.1158/1078-0432.CCR-17-3535

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2019-03-12 xinmeili

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2019-10-17 wangtianj2016@

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2018-12-24 karmond

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2018-12-24 ymljack

#OTC#

104 0
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2018-12-24 wshxjq

#头颈部#

127 0
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2018-12-24 木头人519

#颈部#

101 0
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2018-12-22 医者仁心5538

学习了

119 0

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CLIN CANCER RES：Notch信号功能丧失促进头颈部癌发生

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肿瘤科

CLIN CANCER RES：Notch信号功能丧失促进头颈部癌发生

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