The cellular chloride channels CLIC1 and CLIC4 contribute to virus-mediated cell motility

The Journal of Biological Chemistry
Gabrielė StakaitytėAdrian Whitehouse

Abstract

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 because of the expression of two early regulatory proteins termed small and large tumor antigens (ST and LT, respectively). Several molecular mechanisms have been attributed to MCPyV-mediated 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 ST-induced cell motility and invasiveness. Proteomic analysis revealed that MCPyV ST up-regulates two Cl- channels, CLIC1 and CLIC4, which when silenced, inhibit MCPyV ST-induced motility and invasiveness, implicating their function as critical to MCPyV-induced metastatic processes. Consistent with these data, we conf...Continue Reading

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Citations

Nov 21, 2018·Journal of Leukocyte Biology·Kwan T ChowMichael Gale
Jan 30, 2019·Current Opinion in Oncology·Véronique Del Marmol, Celeste Lebbé
Sep 5, 2019·PLoS Neglected Tropical Diseases·Marietta MüllerAndrew Tuplin
Jun 11, 2019·International Journal of Cancer. Journal International Du Cancer·Satendra KumarWeng-Onn Lui
Mar 3, 2020·Frontiers in Physiology·Shubha Gururaja RaoHarpreet Singh
Dec 18, 2020·Rheumatology·Christopher W WassonFrancesco Del Galdo
Apr 23, 2021·Nano Letters·Ming ChengHaibing Li

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Datasets Mentioned

BETA
GSE39612

Methods Mentioned

BETA
PCR
biopsy
Assay

Software Mentioned

R limma
IncuCyte
Bioconductor
ImageJ
R

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