Morris, Laverick et al., 2018 - EBV-encoded LMP1 induces EMT via CTAR1 through integrin-mediated ERK-MAPK signalling.pdf (4.09 MB)

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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posted on 11.06.2018, 09:03 by Mhairi Morris, Louise Laverick, Wenbin Wei, Alexandra M. Davis, Samantha O'Neill, Liam Wood, Jack Wright, Christopher W. Dawson, Lawrence S. Young
© 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.

Funding

The study was core funded by Cancer Research UK at the University of Birmingham.

History

School

  • Sport, Exercise and Health Sciences

Published in

Cancers

Volume

10

Issue

5

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.

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© The Authors. Published by MDPI

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VoR (Version of Record)

Publisher statement

This work is made available according to the conditions of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) licence. Full details of this licence are available at: https://creativecommons.org/licenses/by-nc-nd/4.0/

Publication date

2018-05-01

Notes

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/

eISSN

2072-6694

Language

en

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