The EBV-Encoded Oncoprotein, LMP1, Induces an Epithelial-to-Mesenchymal Transition (EMT) via Its CTAR1 Domain through Integrin-Mediated ERK-MAPK Signalling.
The EBV-Encoded Oncoprotein, LMP1, Induces an Epithelial-to-Mesenchymal Transition (EMT) via Its CTAR1 Domain through Integrin-Mediated ERK-MAPK Signalling.
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DOI：
10.3390/cancers10050130
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发表时间：
2018-05-01
期刊：
影响因子：
5.2
通讯作者：
Young LS
中科院分区：
文献类型：
--
作者：
Morris MA;Laverick L;Wei W;Davis AM;O'Neill S;Wood L;Wright J;Dawson CW;Young LS
EB病毒（EBV）编码的潜伏膜蛋白1（LMP 1）癌基因可以诱导对上皮细胞的生长和分化，包括上皮细胞间质转化（EMT）的许多特征的深刻影响。为了更好地验证这些作用，我们使用了定义明确的Madin达比犬肾（MDCK）上皮细胞模型，发现这些细胞中的LMP 1表达诱导EMT，如特征性形态学变化所定义的，伴随着E-钙粘蛋白、桥粒钙粘蛋白和紧密连接蛋白表达的丧失。EMT表型的诱导需要LMP 1的功能性CTAR 1结构域，并且使用药理学抑制剂的研究揭示了通常由整合素-配体相互作用诱导的信号传导途径的贡献：细胞外信号调节激酶/促分裂原活化蛋白激酶（ERK-MAPK）、PI 3-激酶和酪氨酸激酶，但不包括转化生长因子β（TGFβ）。更详细的分析表明，在LMP 1诱导的EMT中，CTAR 1介导的Slug和Twist诱导。观察到β1整联蛋白信号传导在LMP 1介导的ERK-MAPK和粘着斑激酶（FAK）磷酸化中的关键作用，并且发现β1整联蛋白活化增强LMP 1诱导的细胞活力和存活。这些发现支持LMP 1通过转录重编程在疾病发病机制中的重要作用，该转录重编程增强肿瘤细胞存活并导致更具侵袭性的转移表型。
The Epstein–Barr virus (EBV)-encoded latent membrane protein 1 (LMP1) oncogene can induce profound effects on epithelial growth and differentiation including many of the features of the epithelial-to-mesenchymal transition (EMT). To better characterise these effects, we used the well-defined Madin Darby Canine Kidney (MDCK) epithelial cell model and found that LMP1 expression in these cells induces EMT as defined by characteristic morphological changes accompanied by loss of E-cadherin, desmosomal cadherin and tight junction protein expression. The induction of the EMT phenotype required a functional CTAR1 domain of LMP1 and studies using pharmacological inhibitors revealed contributions from signalling pathways commonly induced by integrin–ligand interactions: extracellular signal-regulated kinases/mitogen-activated protein kinases (ERK-MAPK), PI3-Kinase and tyrosine kinases, but not transforming growth factor beta (TGFβ). More detailed analysis implicated the CTAR1-mediated induction of Slug and Twist in LMP1-induced EMT. A key role for β1 integrin signalling in LMP1-mediated ERK-MAPK and focal adhesion kianse (FAK) phosphorylation was observed, and β1 integrin activation was found to enhance LMP1-induced cell viability and survival. These findings support an important role for LMP1 in disease pathogenesis through transcriptional reprogramming that enhances tumour cell survival and leads to a more invasive, metastatic phenotype.
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影响因子：
7.3
作者：
Gonzalez DM;Medici D
通讯作者：
Medici D
DOI：
10.1155/2012/248759
发表时间：
2012
期刊：
Journal of signal transduction
影响因子：
--
作者：
Benoit YD;Groulx JF;Gagné D;Beaulieu JF
通讯作者：
Beaulieu JF
影响因子：
5.4
作者：
Dawson, Christopher W.;Laverick, Louise;Young, Lawrence S.
通讯作者：
Young, Lawrence S.
DOI：
10.1142/s0219720005001442
发表时间：
2005-10-01
影响因子：
1
作者：
Breitling, Rainer;Herzyk, Pawel
通讯作者：
Herzyk, Pawel
影响因子：
20.3
作者：
Lajoie, Valerie;Lemieux, Bruno;Knecht, Hans
通讯作者：
Knecht, Hans