Voltage imaging reveals the dynamic electrical signatures of human breast cancer cells
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
Cancer cells feature a resting membrane potential (Vm) that is depolarized compared to normal cells, and express active ionic conductances, which factor directly in their pathophysiological behavior. Despite similarities to ‘excitable’ tissues, relatively little is known about cancer cell Vm dynamics. Here high-throughput, cellular-resolution Vm imaging reveals that Vm fluctuates dynamically in several breast cancer cell lines compared to non-cancerous MCF-10A cells. We characterize Vm fluctuations of hundreds of human triple-negative breast cancer MDA-MB-231 cells. By quantifying their Dynamic Electrical Signatures (DESs) through an unsupervised machine-learning protocol, we identify four classes ranging from "noisy” to “blinking/waving“. The Vm of MDA-MB-231 cells exhibits spontaneous, transient hyperpolarizations inhibited by the voltage-gated sodium channel blocker tetrodotoxin, and by calcium-activated potassium channel inhibitors apamin and iberiotoxin. The Vm of MCF-10A cells is comparatively static, but fluctuations increase following treatment with transforming growth factor-β1, a canonical inducer of the epithelial-to-mesenchymal transition. These data suggest that the ability to generate Vm fluctuations may be a property of hybrid epithelial-mesenchymal cells or those originated from luminal progenitors.
Date Issued
2022-11-11
Date Acceptance
2022-10-05
Citation
Communications Biology, 2022, 5
ISSN
2399-3642
Publisher
Nature Research
Journal / Book Title
Communications Biology
Volume
5
Copyright Statement
© The Author(s) 2022. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
License URL
Sponsor
Royal Academy Of Engineering
Wellcome Trust
Biotechnology and Biological Sciences Research Council (BBSRC)
MRC
Biotechnology and Biological Sciences Research Council (BBSRC)
Grant Number
RF1415\14\26
201964/Z/16/Z
BB/R009007/1
PO :60224942 RE13780 (IBIN3AF)
EP/V520354/1
Subjects
Humans
Cell Line, Tumor
Epithelial-Mesenchymal Transition
Triple Negative Breast Neoplasms
MCF-7 Cells
Membrane Potentials
Cell Line, Tumor
Humans
Membrane Potentials
Epithelial-Mesenchymal Transition
MCF-7 Cells
Triple Negative Breast Neoplasms
Publication Status
Published
Article Number
ARTN 1178