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Updated: Mar 21, 2026
Isolation and Functional Assessment of Human Breast Cancer Stem Cells from Cell and Tissue Samples
Published on: October 2, 2020
Sigma-1 receptors modulate neonatal Nav1.5 ion channels in breast cancer cell lines
Ebru Aydar1, Dan Stratton2, Scott P Fraser3
1Institute of Ophthalmology, University College London, 11/43 Bath Street, London, EC1V 9EL, UK.
Abstract:
The main aim of this study was to investigate a possible functional connection between sigma-1 receptors and voltage-gated sodium channels (VGSCs) in human breast cancer cells. The hypothesis was that sigma-1 drugs could alter the metastatic properties of breast cancer cells via the VGSC. Evidence was found for expression of sigma-1 receptor and neonatal Nav1.5 (nNav1.5) expression in both MDA-MB-231 and MDA-MB-468 cells. Sigma-1 drugs (SKF10047 and dimethyltryptamine) did not affect cell proliferation or migration but significantly reduced adhesion to the substrate. Silencing sigma-1 receptor expression by siRNA similarly reduced the adhesion. Blocking nNav1.5 activity with a polyclonal antibody (NESOpAb) targeting an extracellular region of nNav1.5 also reduced the adhesion in both cell lines. Importantly, the results of combined treatments with NESOpAb and a sigma-1 drug or sigma-1 siRNA suggested that both treatments targeted the same mechanism. The possibility was tested, therefore, that the sigma-1 receptor and the nNav1.5 channel formed a physical, functional complex. This suggestion was supported by the results of co-immunoprecipitation experiments. Furthermore, application of sigma-1 drugs to the cells reduced the surface expression of nNav1.5 protein, which could explain how sigma-1 receptor activation could alter the metastatic behaviour of breast cancer cells. Overall, these results are consistent with the idea of a sigma-1 protein behaving like either a "chaperone" or a regulatory subunit associated with nNav1.5.
Insights
This study reveals a link between sigma-1 receptors and sodium channels in breast cancer cells, showing that targeting this connection reduces cancer cell adhesion and metastasis. These findings suggest a novel therapeutic approach for breast cancer treatment.
Area of Science:
- Cell Biology
- Molecular Biology
- Oncology
Background:
- Sigma-1 receptors and voltage-gated sodium channels (VGSCs) are implicated in cancer progression.
- The specific interaction between sigma-1 receptors and VGSCs in human breast cancer cells remains largely unexplored.
Purpose of the Study:
- To investigate the functional relationship between sigma-1 receptors and VGSCs in human breast cancer cells.
- To determine if targeting this interaction can modulate breast cancer cell metastatic properties.
Main Methods:
- Expression analysis of sigma-1 receptor and neonatal Nav1.5 (nNav1.5) in breast cancer cell lines (MDA-MB-231, MDA-MB-468).
- Treatment with sigma-1 receptor agonists (SKF10047, dimethyltryptamine) and siRNA for sigma-1 receptor.
- Inhibition of nNav1.5 activity using a specific polyclonal antibody (NESOpAb).
- Co-immunoprecipitation assays to assess physical interaction.
Main Results:
- Sigma-1 receptor and nNav1.5 were expressed in MDA-MB-231 and MDA-MB-468 cells.
- Sigma-1 drugs and nNav1.5 inhibition significantly reduced cancer cell adhesion.
- Combined treatments indicated a shared mechanism of action.
- Co-immunoprecipitation confirmed a physical complex between sigma-1 receptor and nNav1.5.
- Sigma-1 drugs decreased surface expression of nNav1.5.
Conclusions:
- A functional and physical association exists between sigma-1 receptors and nNav1.5 in breast cancer cells.
- Sigma-1 receptor activation modulates nNav1.5 surface expression, impacting cancer cell adhesion and potentially metastasis.
- The sigma-1 receptor may act as a chaperone or regulatory subunit for nNav1.5, offering a potential therapeutic target.
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