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|Title: ||The EBV-encoded oncoprotein, LMP1, induces an epithelial-to-mesenchymal transition (EMT) via its CTAR1 domain through integrin-mediated ERK-MAPK signalling|
|Authors: ||Morris, Mhairi A.|
Davis, Alexandra M.
Dawson, Christopher W.
Young, Lawrence S.
Src family kinases
|Issue Date: ||2018|
|Publisher: ||© The Authors. Published by MDPI|
|Citation: ||MORRIS, M.A. ... et al., 2018. The EBV-encoded oncoprotein, LMP1, induces an epithelial-to-mesenchymal transition (EMT) via its CTAR1 domain through integrin-mediated ERK-MAPK signalling. Cancers, 10(5): 130.|
|Abstract: ||© 2018 by the authors. Licensee MDPI, Basel, Switzerland. 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 (TGF β). 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.|
|Description: ||This is an Open Access Article. It is published by MDPI under the Creative Commons Attribution 4.0 Unported Licence (CC BY). Full details of this licence are available at: http://creativecommons.org/licenses/by/4.0/|
|Sponsor: ||The study was core funded by Cancer Research UK at the University of Birmingham.|
|Publisher Link: ||https://doi.org/10.3390/cancers10050130|
|Appears in Collections:||Published Articles (Sport, Exercise and Health Sciences)|
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