Ezrin/NF-κB activation regulates epithelial- mesenchymal transition induced by EGF and promotes metastasis of colorectal cancer
Ezrin/NF-κB activation regulates epithelial- mesenchymal transition induced by EGF and promotes metastasis of colorectal cancer
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Ezrin/NF-κB激活调节EGF诱导的上皮间质转化并促进结直肠癌转移
DOI：
10.1016/j.biopha.2017.05.058
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发表时间：
2017-08-01
影响因子：
7.5
通讯作者：
Wang, Youyuan
中科院分区：
文献类型：
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作者：
Li, Yingru;Lin, Zhaoyu;Wang, Youyuan
越来越多的证据表明上皮间质转化（EMT）在肿瘤转移中起着重要作用。诱导肿瘤细胞EMT的细胞因子有很多，EGF是其中重要的一种。Ezrin是细胞骨架与细胞膜之间的连接蛋白，与肿瘤细胞的形态运动和转移密切相关。EGF可以激活Ezrin并影响细胞运动。近年来的研究表明，NF-κ B B作为一种重要的转录因子，参与了EMT的发生、发展过程。然而，Ezrin是否通过NF-κ B B通路参与EGF诱导的EMT的调节？这个问题需要我们讨论。在本研究中，我们发现EGF可以诱导大肠癌细胞发生EMT，增强其侵袭和迁移能力，并促进Ezrin Tyr 353的磷酸化。另一方面，抑制Ezrin可逆转EGF诱导的EMT，并抑制NF-κ B B P65向细胞核的转位。Ezrin基因敲除可抑制EGF诱导的结直肠癌肺转移，Ezrin和NF-κ B的异常激活与结直肠癌转移和预后不良有关。本研究结果提示Ezrin/NF-κ B通路可能为大肠癌转移靶向治疗提供实验依据。(C)2017年Elsevier Masson SAS。All rights reserved.
There is growing evidence that epithelial mesenchymal-transition (EMT) plays significant roles in terms of tumor metastasis. There are a lot of cytokines inducing EMT of tumor cells, EGF is one of the important cytokines. Ezrin is a connexin between the cytoskeleton and the cell membrane, which is closely related to the morphological movement and metastasis of tumor cells. EGF can activate Ezrin and affects cell motility. In recent years, many studies have shown that NF-kappa B acts as an important transcription factor, involving in the process of EMT. However, does Ezrin participate in the regulation of EGF-induced EMT through the NF-kappa B pathway? This question needs us to discuss. In the present study, we found that EGF could induce colorectal cancer cells to develop EMT, enhance their ability to invade and migrate and promotes phosphorylation of Ezrin Tyr353. On the other hand, inhibition of Ezrin could reverse EGF-induced EMT and inhibit NF-kappa B P65 translocating into the nucleus. Finally, knockout of Ezrin inhibited EGF-induced lung metastasis of colorectal cancer xenografts and abnormal activation of Ezrin and NF-kappa B were related with colorectal cancer metastasis and poor prognosis. Our present results suggest that Ezrin/NF-kappa B pathway may provide experimental evidence for new targeted drugs for colorectal cancer metastasis. (C) 2017 Elsevier Masson SAS. All rights reserved.