Yoshida Ryoji, Ito Takaaki, Hassan Wael Abdo, Nakayama Hideki
Department of Oral and Maxillofacial Surgery, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan.
Department of Pathology and Experimental Medicine, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan.
Histol Histopathol. 2017 Apr;32(4):315-323. doi: 10.14670/HH-11-821. Epub 2016 Sep 12.
Notch signaling has been reported to be involved in several types of malignant tumors. However, the role and activation mechanisms of Notch signaling in oral squamous cell carcinoma (OSCC) remain poorly characterized. The present review focuses on the dual role of Notch signaling in OSCC. A number of expression and functional analyses demonstrated that Notch1 plays a crucial role in development and progression of OSCC. On the other hand, a tumor suppressive role of Notch1 was also suggested from studies, based on deep sequencing of cancer genomes. Interestingly, although some Notch1 mutations overlap in tumors from Caucasian and Asian patients, the overall spectrum of such mutations is vastly different between these cohorts. Accumulating evidence suggests that variation of Notch1 mutation signature may determine the role of Notch signaling in OSCC. As Notch is thought to act as an oncogene in a subset of OSCC, but also has a tumor suppression role, the role of Notch in OSCC seems to be highly context dependent.
据报道，Notch信号通路参与多种类型的恶性肿瘤。然而，Notch信号通路在口腔鳞状细胞癌（OSCC）中的作用和激活机制仍不清楚。本综述聚焦于Notch信号通路在OSCC中的双重作用。多项表达和功能分析表明，Notch1在OSCC的发生和发展中起关键作用。另一方面，基于癌症基因组深度测序的研究也提示了Notch1的肿瘤抑制作用。有趣的是，尽管白种人和亚洲患者肿瘤中的一些Notch1突变存在重叠，但这些队列中此类突变的总体谱却大不相同。越来越多的证据表明，Notch1突变特征的差异可能决定Notch信号通路在OSCC中的作用。由于Notch在一部分OSCC中被认为是一种癌基因，但也具有肿瘤抑制作用，Notch在OSCC中的作用似乎高度依赖于背景。
