期刊
LABORATORY INVESTIGATION
卷 93, 期 10, 页码 1068-1081出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/labinvest.2013.95
关键词
invasion; Notch signaling; oral squamous cell carcinoma; TNF-alpha; proliferation
资金
- Ministry of Education, Culture, Sports, Science and Technology of Japan [21590440]
- Grants-in-Aid for Scientific Research [21590440] Funding Source: KAKEN
Notch signaling has been reported to be involved in several types of malignant tumors; however, the role and activation mechanism of Notch signaling in oral squamous cell carcinoma (OSCC) remains poorly characterized. The purpose of this study was to elucidate the pathological significance of Notch signaling and its activation mechanism in the development and progression of OSCC. In this study, we showed that the expression of Notch1 and intracellular Notch domain (NICD) are upregulated in OSCCs. In addition, Notch1 and NICD were found to be characteristically localized at the invasive tumor front. TNF-alpha, a major inflammatory cytokine, significantly activated Notch signaling in vitro. In a clinicopathological analysis, Notch1 expression correlated with both the T-stage and the clinical stage. Furthermore, loss of Notch1 expression correlated with the inhibition of cell proliferation and TNF-alpha-dependent invasiveness in an OSCC cell line. In addition, gamma-secretase inhibitor (GSI) prevented cell proliferation and TNIF-alpha-dependent invasion of OSCC cells in vitro. These results indicate that altered expression of Notch1 is associated with increased cancer progression and that Notch1 regulates the steps involved in cell metastasis in OSCC. Moreover, inactivating Notch signaling with GSI could therefore be a useful approach for treating patients with OSCC.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据