期刊
BRITISH JOURNAL OF CANCER
卷 110, 期 3, 页码 695-705出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/bjc.2013.770
关键词
tongue squamous cell carcinoma; metastasis; Ezrin; EMT; NF-kappa B
类别
资金
- National Natural Science Foundation of China [81172563, 81072225, 81272951]
- Natural Science Foundation of Guangdong Province [S2011010003979, 10251008901000022]
- Specialized Research Fund for the Doctoral Program of Higher Education [20110171110068]
- Science and Technology Project of Guangzhou City [11C22060035]
- China Postdoctoral Science Foundation [2012M521649]
Background: Epithelial-mesenchymal transition (EMT) is a crucial programme in cancer metastasis. Epidermal growth factor (EGF) is a key inducer of EMT, and Ezrin has an important role in this process. However, how Ezrin is activated and whether it mediates EGF-induced EMT in tongue squamous cell carcinomas (TSCCs) through activating NF-kappa B remains obscure. Methods: We used two TSCC cell lines as a cell model to study invasion and EMT in vitro, and used nude mice xenografts model to evaluate metastasis of TSCC cells. Finally, we evaluated the level of pEzrin Tyr353, nuclear p65 and EMT markers in TSCC clinical samples. Results: Ezrin Tyr353 was phosphorylated through Akt (but not ERK1/2, ROCK1) pathway, and lead to the activation of NF-kappa B in EGF-treated TSCC cells. Akt and NF-kappa B inhibitors blocked EGF-induced EMT, and suppressed invasion and migration of TSCC cells. In vivo, silencing Ezrin significantly suppressed EGF-enhanced metastasis of TSCC xenografts. Finally, high levels of expression of pEzrin Tyr353, nuclear p65, vimentin and low level of expression of E-cadherin were correlated with cancer metastasis and poor patient prognosis. Conclusion: Our data suggest that Akt/Ezrin Tyr353/NF-kappa B pathway regulates EGF-induced EMT and metastasis inTSCC, and Ezrin may serve as a therapeutic target to reverse EMT in tongue cancers and prevent TSCC progression.
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