Voltage-Gated Sodium Channel Expression and Potentiation of Human Breast Cancer Metastasis

dc.contributor.author Koyutürk, Meral
dc.date.accessioned 2021-02-19T10:14:35Z
dc.date.available 2021-02-19T10:14:35Z
dc.date.issued 2005
dc.description.abstract Purpose: Ion channel activity is involved in several basic cellular behaviors that are integral to metastasis (e.g., proliferation, motility, secretion, and invasion), although their contribution to cancer progression has largely been ignored. The purpose of this study was to investigate voltage-gated Na + channel (VGSC) expression and its possible role in human breast cancer. Experimental Design: Functional VGSC expression was investigated in human breast cancer cell lines by patch clamp recording. The contribution of VGSC activity to directional motility, endocytosis, and invasion was evaluated by in vitro assays. Subsequent identification of the VGSC α-subunit(s) expressed in vitro was achieved using reverse transcription-PCR, immunocytochemistry, and Western blot techniques and used to investigate VGSCα expression and its association with metastasis in vivo. Results: VGSC expression was significantly up-regulated in metastatic human breast cancer cells and tissues, and VGSC activity potentiated cellular directional motility, endocytosis, and invasion. Reverse transcription-PCR revealed that Na v1.5, in its newly identified "neonatal" splice form, was specifically associated with strong metastatic potential in vitro and breast cancer progression in vivo. An antibody specific for this form confirmed up-regulation of neonatal Na v1.5 protein in breast cancer cells and tissues. Furthermore, a strong correlation was found between neonatal Na v1.5 expression and clinically assessed lymph node metastasis. Conclusions: Up-regulation of neonatal Na v1.5 occurs as an integral part of the metastatic process in human breast cancer and could serve both as a novel marker of the metastatic phenotype and a therapeutic target. en_US
dc.identifier.citationcount 362
dc.identifier.doi 10.1158/1078-0432.CCR-05-0327 en_US
dc.identifier.endpage 5389 en_US
dc.identifier.issn 1078-0432 en_US
dc.identifier.issn 1078-0432
dc.identifier.issue 15 en_US
dc.identifier.pmid 16061851 en_US
dc.identifier.scopus 2-s2.0-23044441734 en_US
dc.identifier.scopusquality Q1
dc.identifier.startpage 5381 en_US
dc.identifier.uri https://hdl.handle.net/20.500.12469/3951
dc.identifier.volume 11 en_US
dc.identifier.wos WOS:000230878900009 en_US
dc.identifier.wosquality Q1
dc.institutionauthor Koyutürk, Meral en_US
dc.language.iso en en_US
dc.relation.journal Clinical Cancer Research en_US
dc.relation.publicationcategory Makale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı en_US
dc.rights info:eu-repo/semantics/openAccess en_US
dc.scopus.citedbyCount 408
dc.subject Ion channel en_US
dc.subject Voltage gated sodium channel en_US
dc.title Voltage-Gated Sodium Channel Expression and Potentiation of Human Breast Cancer Metastasis en_US
dc.type Article en_US
dc.wos.citedbyCount 389
dspace.entity.type Publication

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