Voltage-Gated Sodium Channel Expression and Potentiation of Human Breast Cancer Metastasis
Open accessAbstract
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 alpha-subunit(s) expressed in vitro was achieved using reverse transcription-PCR, immunocytochemistry, and Western blot techniques and used to investigate VGSCalpha 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(v)1.5, 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(v)1.5 protein in breast cancer cells and tissues. Furthermore, a strong correlation was found between neonatal Na(v)1.5 expression and clinic…
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Both these values are more depolarized than normal breast cells, e.g., the mean Vm of unsynchronized MCF-10A cells is between −40 and −58 mV.
“Both these values are more depolarized than normal breast cells, e.g., the mean Vm of unsynchronized MCF-10A cells is between −40 and −58 mV (Marino et al., 1994; Wonderlin et al., 1995; Fraser et al., 2005).”
From Membrane potential and cancer progression (2013) · cites this paper as Fraser et al., 2005
Functional VGSCs have been found in a number of cancer types, and suppressing VGSCs with siRNA or pharmacological agents inhibits migration and invasion.
“For example, functional VGSCs have been found in a number of cancer types [reviewed in Brackenbury (2012)], and suppressing VGSCs with siRNA or pharmacological agents inhibits migration and invasion (Roger et al., 2003; Fraser et al., 2005; Brackenbury et al., 2007; House et al., 2010; Yang et al., 2012).”
From Membrane potential and cancer progression (2013) · cites this paper as Fraser et al., 2005
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Membrane potential and cancer progression
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- Authors
- Fraser, S. P., Diss, J. K. J., Chioni, A.-M., Mycielska, M. E., Pan, H., Yamaci, R. F., Pani, F., Siwy, Z., Krasowska, M., Grzywna, Z., Brackenbury, W. J., Theodorou, D., Koyutürk, M., Kaya, H., Battaloglu, E., De Bella, M. T., Slade, M. J., Tolhurst, R., Palmieri, C., Jiang, J., Latchman, D. S., Coombes, R. C., & Djamgoz, M. B. A.
- Affiliations
- Imperial College London (GB)
- Institute of Child Health (IN)
- Boğaziçi University (TR)
- Silesian University of Technology (PL)
- 5Department of Histology and Embryology, Kadir Has University;
- Marmara University (TR)
- 4Department of Molecular Biology and Genetics, Bogazici University;
- 3Department of Cancer Medicine, CRC Laboratories, Medical Research Council Cyclotron Building, Imperial College School of Medicine, London, United Kingdom;
- ORCID
- Venue
- Clinical Cancer Research
- Published
- 2005-08-01
- Volume
- 11
- Issue
- 15
- Pages
- 5381-5389
- ISSN
- 1078-0432 (ISSN-L)
- 1557-3265
- OpenAlex
- W2114016572
- Cited by
- 481
- References
- 0
- Citations by year
- 2026: 15 · 2025: 27 · 2024: 24 · 2023: 15 · 2022: 34 · 2021: 31 · 2020: 39 · 2019: 40 · 2018: 28 · 2017: 18 · 2016: 14 · 2015: 28 · 2014: 32 · 2013: 23 · 2012: 24
- FWCI
- 5.42
- Type
- journal article
- Language
- en
- Open access
- Licence
- other-oa
- Locations
- Clinical Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- Dspace Repository (Marmara Üniversitesi) (submittedVersion, other-oa)
- UCL Discovery (University College London) (submittedVersion)
- Dspace Repository (Marmara Üniversitesi) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mechanisms of cancer metastasis
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Keywords
- voltage-gated sodium channels, breast cancer metastasis, directional motility, cell invasion, endocytosis, lymph node metastasis, metastatic markers, therapeutic target
- MeSH terms
- Amino Acid Sequence, Biopsy, Breast, Breast Neoplasms, Cell Movement, Dose-Response Relationship, Drug, Electrophysiology, Endocytosis, Epithelial Cells, Humans, Immunohistochemistry, Ions, Lymphatic Metastasis, Molecular Sequence Data, Neoplasm Invasiveness, Neoplasm Metastasis, Phenotype, Tetrodotoxin, Blotting, Western, Sodium Channels, Up-Regulation, Gene Expression Regulation, Neoplastic, Patch-Clamp Techniques, Disease Progression, Protein Isoforms, Reverse Transcriptase Polymerase Chain Reaction, Cell Line, Tumor, Cell Proliferation, NAV1.5 Voltage-Gated Sodium Channel, In Vitro Techniques
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