Epstein-Barr Virus latent membrane protein 1 induces Snail and epithelial-mesenchymal transition in metastatic nasopharyngeal carcinoma.

Epstein-Barr Virus latent membrane protein 1 induces Snail and epithelial-mesenchymal transition in metastatic nasopharyngeal carcinoma.
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DOI:
10.1038/bjc.2011.38
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发表时间:
2011-03-29
影响因子:
8.8
通讯作者:
Pagano, J. S.
Pagano, J. S.
中科院分区:
医学1区
文献类型:
--
作者:
Horikawa, T.;Yoshizaki, T.;Kondo, S.;Furukawa, M.;Kaizaki, Y.;Pagano, J. S.

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EB病毒(EBV)相关的鼻咽癌(NPC)是头颈部肿瘤中的一种特殊类型,其组织病理学特点是未分化和高转移。我们最近研究了上皮间质转化(EMT)在鼻咽癌中的作用。在先前的研究中,我们发现EBV主要癌蛋白LMP 1的表达与Twist的表达和EMT的诱导密切相关。应用免疫组化方法检测41例鼻咽癌组织中Snail的表达。以NP 69 SV 40 T人鼻咽癌细胞为研究对象,探讨Twist和Snail在鼻咽癌EMT中的作用。在NPC组织中,Snail的过表达与癌细胞中LMP 1的表达相关。Snail的表达与转移呈正相关,与E-cadherin的表达呈独立负相关。Twist的表达与E-cadherin的表达无相关性。此外,在人鼻咽细胞系中,LMP 1诱导EMT及其相关的细胞运动性和侵袭性。在这些细胞中,LMP 1诱导Snail的表达,并且针对Snail的小发夹RNA(shRNA)逆转了细胞变化。相比之下,Twist在这些鼻咽细胞中不产生EMT。这项研究加强了EMT与NPC转移行为的相关性。这些结果表明,由EBV癌蛋白LMP 1诱导的Snail在NPC的EMT中具有关键作用。
Epstein-Barr Virus (EBV)-associated nasopharyngeal carcinoma (NPC) is distinctive among head-and-neck cancers in its undifferentiated histopathology and highly metastatic character. We have recently investigated the involvement of epithelial–mesenchymal transition (EMT) in NPC. In a previous study, we found a close association of expression of LMP1, the principal EBV oncoprotein, with expression of Twist and induction of EMT. We analysed expression of Snail in 41 NPC tissues by immunohistochemistry. The role of Twist as well as Snail in EMT of NPC was investigated by using NP69SV40T human nasopharyngeal cells. In NPC tissues, overexpression of Snail is associated with expression of LMP1 in carcinomatous cells. In addition, expression of Snail positively correlated with metastasis and independently correlated inversely with expression of E-cadherin. Expression of Twist had no association with expression of E-cadherin. Further, in a human nasopharyngeal cell line, LMP1 induces EMT and its associated cellular motility and invasiveness. Expression of Snail is induced by LMP1 in these cells, and small hairpin RNA (shRNA) to Snail reversed the cellular changes. By contrast, Twist did not produce EMT in these nasopharyngeal cells. This study strengthens the association of EMT with the metastatic behaviour of NPC. These results suggest that induction of Snail by the EBV oncoprotein LMP1 has a pivotal role in EMT in NPC.
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