Akt/Ezrin Tyr353/NF-κB pathway regulates EGF-induced EMT and metastasis in tongue squamous cell carcinoma.
Akt/Ezrin Tyr353/NF-κB pathway regulates EGF-induced EMT and metastasis in tongue squamous cell carcinoma.
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DOI：
10.1038/bjc.2013.770
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发表时间：
2014-02-04
影响因子：
8.8
通讯作者：
Chen, W.
中科院分区：
文献类型：
--
作者：
Wang, Y.;Lin, Z.;Sun, L.;Fan, S.;Huang, Z.;Zhang, D.;Yang, Z.;Li, J.;Chen, W.
上皮-间质转化（Epithelial-mesenchymal transition， EMT）是肿瘤转移的关键过程。表皮生长因子（EGF）是EMT的关键诱导剂，Ezrin在这一过程中起着重要作用。然而，Ezrin如何被激活以及它是否通过激活NF-κB介导egf诱导的舌鳞癌（TSCCs） EMT尚不清楚。我们以两种TSCC细胞系为细胞模型，在体外研究侵袭和EMT，并采用裸鼠异种移植模型评估TSCC细胞的转移。最后，我们评估了TSCC临床样本中pEzrin Tyr353、核p65和EMT标志物的水平。Ezrin Tyr353通过Akt（而不是ERK1/2， ROCK1）途径磷酸化，并导致egf处理的TSCC细胞中NF-κB的激活。Akt和NF-κB抑制剂阻断egf诱导的EMT，抑制TSCC细胞的侵袭和迁移。在体内，沉默Ezrin可显著抑制egf增强的TSCC移植物转移。最后，pEzrin Tyr353、nuclear p65、vimentin的高表达和E-cadherin的低表达与肿瘤转移和患者预后不良相关。我们的数据表明，Akt/Ezrin Tyr353/NF-κB通路调节egf诱导的EMT和转移的inTSCC， Ezrin可能作为逆转舌癌EMT和阻止TSCC进展的治疗靶点。
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-κB remains obscure. 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. Ezrin Tyr353 was phosphorylated through Akt (but not ERK1/2, ROCK1) pathway, and lead to the activation of NF-κB in EGF-treated TSCC cells. Akt and NF-κB 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. Our data suggest that Akt/Ezrin Tyr353/NF-κB 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.
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影响因子：
254.7
作者：
Jemal, Ahmedin;Siegel, Rebecca;Thun, Michael J.
通讯作者：
Thun, Michael J.
DOI：
10.1186/bcr1006
发表时间：
2005
期刊：
Breast cancer research : BCR
影响因子：
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作者：
Elliott BE;Meens JA;SenGupta SK;Louvard D;Arpin M
通讯作者：
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影响因子：
4
作者：
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通讯作者：
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影响因子：
2.5
作者：
Hardy, Katharine M.;Booth, Brian W.;Hendrix, Mary J. C.;Salomon, David S.;Strizzi, Luigi
通讯作者：
Strizzi, Luigi
影响因子：
8
作者：
Chuan, Y-C;Iglesias-Gato, D.;Flores-Morales, A.
通讯作者：
Flores-Morales, A.