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dc.contributor.authorStakaityte, G.*
dc.contributor.authorNwogu, N.*
dc.contributor.authorLippiat, J.D.*
dc.contributor.authorBlair, G.E.*
dc.contributor.authorPoterlowicz, Krzysztof*
dc.contributor.authorBoyne, James R.*
dc.contributor.authorMacdonald, A.*
dc.contributor.authorMankouri, J.*
dc.contributor.authorWhitehouse, A.*
dc.date.accessioned2018-02-23T11:47:14Z
dc.date.available2018-02-23T11:47:14Z
dc.date.issued2018-03
dc.identifier.citationStakaityte G, Nwogu N, Lippiat JD et al (2018) The cellular chloride channels CLIC1 and CLIC4 contribute to virus-mediated cell motility. Journal of Biological Chemistry. 293(12): 4582-4590.en_US
dc.identifier.urihttp://hdl.handle.net/10454/15061
dc.descriptionYesen_US
dc.description.abstractIon channels regulate many aspects of cell physiology, including cell proliferation, motility, and migration, and aberrant expression and activity of ion channels is associated with various stages of tumor development, with K+ and Cl- channels now being considered the most active during tumorigenesis. Accordingly, emerging in vitro and preclinical studies have revealed that pharmacological manipulation of ion channel activity offers protection against several cancers. Merkel cell polyomavirus (MCPyV) is a major cause of Merkel cell carcinoma (MCC), primarily due to the expression of two early regulatory proteins termed small and large tumour antigens (ST and LT, respectively). Several molecular mechanisms have been attributed to MCPyVmediated cancer formation but thus far, no studies have investigated any potential link to cellular ion channels. Here we demonstrate that Cl- channel modulation can reduce MCPyV STinduced cell motility and invasiveness. Proteomic analysis revealed that MCPyV ST upregulates two Cl- channels; CLIC1 and CLIC4, which when silenced, inhibit MCPyV STinduced motility and invasiveness, implicating their function as critical to MCPyV-induced metastatic processes. Consistent with these data, we confirmed that CLIC1 and CLIC4 are upregulated in primary MCPyV-positive MCC patient samples. We therefore, for the first time, implicate cellular ion channels as a key host cell factor contributing to virus-mediated cellular transformation. Given the intense interest in ion channel modulating drugs for human disease, this highlights CLIC1 and CLIC4 activity as potential targets for MCPyV-induced MCC.en_US
dc.description.sponsorshipBBSRC DTP studentship (BB/J014443/1) and Royal Society University Research Fellowship to JM (UF100419)en_US
dc.language.isoenen_US
dc.rights© 2018 by The American Society for Biochemistry and Molecular Biology, Inc. Reproduced in accordance with the publisher's self-archiving policy. Author's Choice—Final version free via Creative Commons CC-BY license.en_US
dc.subjectCell motility; Cell migration; Channel activation; Chloride channel; Viral proteinen_US
dc.titleThe cellular chloride channels CLIC1 and CLIC4 contribute to virus-mediated cell motilityen_US
dc.status.refereedYesen_US
dc.date.Accepted2018-02-08
dc.date.application2018-02-08
dc.typeArticleen_US
dc.type.versionAccepted Manuscripten_US
dc.identifier.doihttps://doi.org/10.1074/jbc.RA117.001343
refterms.dateFOA2018-07-28T03:08:42Z


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