Show simple item record

dc.contributor.authorNwogu, N.
dc.contributor.authorBoyne, James R.
dc.contributor.authorDobson, S.J.
dc.contributor.authorPoterlowicz, Krzysztof
dc.contributor.authorBlair, G.E.
dc.contributor.authorMacdonald, A.
dc.contributor.authorMankouri, J.
dc.contributor.authorWhitehouse, A.
dc.date.accessioned2018-09-21T12:56:39Z
dc.date.available2018-09-21T12:56:39Z
dc.identifier.citationNwogu N, Boyne JR, Dobson SJ, Poterlowicz K, Blair GE, Macdonald A, Mankouri J and Whitehouse A (2018) Cellular sheddases are induced by Merkel cell polyomavirus small tumour antigen to mediate cell dissociation and invasiveness. PLoS Pathogens. 14(9): e1007276.en_US
dc.identifier.urihttp://hdl.handle.net/10454/16579
dc.descriptionyes
dc.description.abstractMerkel cell carcinoma (MCC) is an aggressive skin cancer with a high propensity for recurrence and metastasis. Merkel cell polyomavirus (MCPyV) is recognised as the causative factor in the majority of MCC cases. The MCPyV small tumour antigen (ST) is considered to be the main viral transforming factor, however potential mechanisms linking ST expression to the highly metastatic nature of MCC are yet to be fully elucidated. Metastasis is a complex process, with several discrete steps required for the formation of secondary tumour sites. One essential trait that underpins the ability of cancer cells to metastasise is how they interact with adjoining tumour cells and the surrounding extracellular matrix. Here we demonstrate that MCPyV ST expression disrupts the integrity of cell-cell junctions, thereby enhancing cell dissociation and implicate the cellular sheddases, A disintegrin and metalloproteinase (ADAM) 10 and 17 proteins in this process. Inhibition of ADAM 10 and 17 activity reduced MCPyV ST-induced cell dissociation and motility, attributing their function as critical to the MCPyV-induced metastatic processes. Consistent with these data, we confirm that ADAM 10 and 17 are upregulated in MCPyV-positive primary MCC tumours. These novel findings implicate cellular sheddases as key host cell factors contributing to virus-mediated cellular transformation and metastasis. Notably, ADAM protein expression may be a novel biomarker of MCC prognosis and given the current interest in cellular sheddase inhibitors for cancer therapeutics, it highlights ADAM 10 and 17 activity as a novel opportunity for targeted interventions for disseminated MCC.en_US
dc.description.sponsorshipIn parts by the Medical Research Council (95505126) to AW, Royal Society (UF100419) to JM and Biotechnology and Biological Sciences Research Council (BB/R000352/1) to GEB and AW.en_US
dc.language.isoenen_US
dc.relation.isreferencedbyhttps://doi.org/10.1371/journal.ppat.1007276en_US
dc.rights© 2018 Nwogu et al. Published by PLOS. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
dc.subjectMerkel cell carcinoma (MCC)en_US
dc.subjectSkin canceren_US
dc.subjectMerkel cell polyomavirus (MCPyV)en_US
dc.subjectCellular sheddasesen_US
dc.subjectCancer therapeuticsen_US
dc.subjectInvasivenessen_US
dc.subjectCell dissociationen_US
dc.titleCellular sheddases are induced by Merkel cell polyomavirus small tumour antigen to mediate cell dissociation and invasivenessen_US
dc.status.refereedyesen_US
dc.date.Accepted2018-08-10
dc.typeArticleen_US
dc.type.versionpublished version paperen_US
refterms.dateFOA2018-09-21T12:56:43Z


Item file(s)

Thumbnail
Name:
Nwogu Boyne 2018 et al.pdf
Size:
8.839Mb
Format:
PDF
Description:
Keep suppressed - final draft - ...
Thumbnail
Name:
journal.ppat.1007276.pdf
Size:
8.486Mb
Format:
PDF
Description:
Main article

This item appears in the following Collection(s)

Show simple item record