The Epstein-Barr virus encoded LMP1 oncoprotein modulates cell adhesion via regulation of activin A/TGFβ and β1 integrin signalling
journal contributionposted on 31.01.2018, 11:39 by Mhairi MorrisMhairi Morris, Christopher W. Dawson, Louise Laverick, Alexandra M. Davis, Joe P. Dudman, Sathuwarman Raveenthiraraj, Zeeshan Ahmad, Lee-Fah Yap, Lawrence S. Young
Approximately 20% of global cancer incidence is causally linked to an infectious agent. EpsteinBarr virus (EBV) accounts for around 1% of all virus-associated cancers and is associated with nasopharyngeal carcinoma (NPC). Latent membrane protein 1 (LMP1), the major oncoprotein encoded by EBV, behaves as a constitutively active tumour necrosis factor (TNF) receptor activating a variety of signalling pathways, including the three classic MAPKs (ERK-MAPK, p38 MAPK and JNK/SAPK). The present study identifes novel signalling properties for this integral membrane protein via the induction and secretion of activin A and TGFβ1, which are both required for LMP1’s ability to induce the expression of the extracellular matrix protein, fbronectin. However, it is evident that LMP1 is unable to activate the classic Smad-dependent TGFβ signalling pathway, but rather elicits its efects through the non-Smad arm of TGFβ signalling. In addition, there is a requirement for JNK/SAPK signalling in LMP1-mediated fbronectin induction. LMP1 also induces the expression and activation of the major fbronectin receptor, α5β1 integrin, an efect that is accompanied by increased focal adhesion formation and turnover. Taken together, these fndings support the putative role for LMP1 in the pathogenesis of NPC by contributing to the metastatic potential of epithelial cells.
Medical Research Council, Cancer Research UK and the European Commission’s FP6 Life Sciences Health Programme (INCA project LSHC-CT-2005-018704) at the University of Birmingham (for MM, LL, LY and CD), High Impact Research Grant UM.C/625/1/HIR/MOHE/DENT/22&23 from the University of Malaya (LFY), and De Montfort University (for MM, AD, JD, SR and ZA).
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