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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.
Laverick, Louise
Wei, Wenbin
Davis, Alexandra M.
O'Neill, Samantha
Wood, Liam
Wright, Jack
Dawson, Christopher W.
Young, Lawrence S.
Keywords: EBV
Src family kinases
β1 integrins
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.
Version: Published
DOI: 10.3390/cancers10050130
URI: https://dspace.lboro.ac.uk/2134/33363
Publisher Link: https://doi.org/10.3390/cancers10050130
Appears in Collections:Published Articles (Sport, Exercise and Health Sciences)

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