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Potassium channel-driven bioelectric signaling regulates metastasis in triple-negative breast cancer

View ORCID ProfileSamantha L Payne, Priyanka Ram, Deepti H. Srinivasan, Thanh T. Le, View ORCID ProfileMichael Levin, View ORCID ProfileMadeleine J Oudin
doi: https://doi.org/10.1101/2021.04.06.438714
Samantha L Payne
1Department of Biomedical Engineering, 200 College Avenue, Tufts University, Medford MA 02155, USA
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Priyanka Ram
1Department of Biomedical Engineering, 200 College Avenue, Tufts University, Medford MA 02155, USA
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Deepti H. Srinivasan
1Department of Biomedical Engineering, 200 College Avenue, Tufts University, Medford MA 02155, USA
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Thanh T. Le
1Department of Biomedical Engineering, 200 College Avenue, Tufts University, Medford MA 02155, USA
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Michael Levin
2Allen Discovery Center, 200 College Avenue, Tufts University, Medford, MA 02155, USA
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Madeleine J Oudin
1Department of Biomedical Engineering, 200 College Avenue, Tufts University, Medford MA 02155, USA
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  • For correspondence: madeleine.oudin@tufts.edu
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Abstract

There is a critical need to better understand the mechanisms that drive local cell invasion and metastasis to develop new therapeutics targeting metastatic disease. Bioelectricity is an important mediator of cellular processes and changes in the resting membrane potential (RMP) are associated with increased cancer cell invasion. However, the mechanism is not well understood. Our data demonstrate that altering the RMP of triple-negative breast cancer (TNBC) cells by manipulating potassium channel expression increases in vitro invasion, in vivo tumor growth, and metastasis, and is accompanied by changes in gene expression associated with cell adhesion. We describe a novel mechanism for RMP-mediated cell migration involving cadherin-11 and the MAPK pathway. Importantly, we identify a new strategy to target metastatic TNBC in vivo by repurposing FDA-approved potassium channel blockers. Our results provide an understanding of the mechanisms by which bioelectricity regulates cancer cell invasion and metastasis that could lead to a new class of therapeutics for patients with metastatic disease.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted April 06, 2021.
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Potassium channel-driven bioelectric signaling regulates metastasis in triple-negative breast cancer
Samantha L Payne, Priyanka Ram, Deepti H. Srinivasan, Thanh T. Le, Michael Levin, Madeleine J Oudin
bioRxiv 2021.04.06.438714; doi: https://doi.org/10.1101/2021.04.06.438714
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Potassium channel-driven bioelectric signaling regulates metastasis in triple-negative breast cancer
Samantha L Payne, Priyanka Ram, Deepti H. Srinivasan, Thanh T. Le, Michael Levin, Madeleine J Oudin
bioRxiv 2021.04.06.438714; doi: https://doi.org/10.1101/2021.04.06.438714

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