Yes / Ion 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. / BBSRC DTP studentship (BB/J014443/1) and Royal Society University Research Fellowship to JM (UF100419)
| Identifer | oai:union.ndltd.org:BRADFORD/oai:bradscholars.brad.ac.uk:10454/15061 |
| Date | 02 August 2018 |
| Creators | Stakaityte, G., Nwogu, N., Lippiat, J.D., Blair, G.E., Poterlowicz, Krzysztof, Boyne, James R., Macdonald, A., Mankouri, J., Whitehouse, A. |
| Source Sets | Bradford Scholars |
| Language | English |
| Detected Language | English |
| Type | Article, Accepted manuscript |
| 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., CC-BY |
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