Membrane voltage fluctuations in human breast cancer cells

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. With high-throughput, cellular-resolution Vm imaging, we characterized Vm fluctuations of hundreds of human triple-negative breast cancer MDA-MB-231 cells and compared to non-cancerous breast epithelial MCF-10A cells. By quantifying their Dynamic Electrical Signatures (DESs) through an unsupervised machine-learning protocol, we identified four classes ranging from "noisy" to "blinking/waving". The Vm of MDA-MB-231 cells exhibited spontaneous, transient hyperpolarizations that were inhibited by the voltage-gated sodium channel blocker tetrodotoxin. The Vm of MCF-10A cells was comparatively static, but fluctuations increased 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 is acquired during transformation and may participate in oncogenesis.

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Abstract P4-06-14: Induction of Blimp-1 in Breast Cancer Cells Is Mediated by Activator Protein-1 and Promotes Transforming Growth Factor (TGF)-ß-Induced Epithelial-to-Mesenchymal Transition

10.1158/0008-5472.sabcs10-p4-06-14 ◽

2010 ◽

Author(s):

M Romagnoli ◽

K Belguise ◽

X Wang ◽

GE. Sonenshein

Keyword(s):

Breast Cancer ◽

Growth Factor ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Epithelial To Mesenchymal Transition ◽

Transforming Growth Factor ◽

Activator Protein 1 ◽

Mesenchymal Transition ◽

Activator Protein

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Expression of Cox-2 in human breast cancer cells as a critical determinant of epithelial-to-mesenchymal transition and invasiveness

Expert Opinion on Therapeutic Targets ◽

10.1517/14728222.2014.860447 ◽

2013 ◽

Vol 18 (2) ◽

pp. 121-135 ◽

Cited By ~ 69

Author(s):

Claudia Bocca ◽

Monica Ievolella ◽

Riccardo Autelli ◽

Manuela Motta ◽

Luciano Mosso ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Human Breast Cancer ◽

Breast Cancer Cells ◽

Epithelial To Mesenchymal Transition ◽

Human Breast Cancer Cells ◽

Human Breast ◽

Critical Determinant ◽

Mesenchymal Transition ◽

Cox 2

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Rab31-dependent regulation of transforming growth factor ß expression in breast cancer cells

Molecular Medicine ◽

10.1186/s10020-021-00419-8 ◽

2021 ◽

Vol 27 (1) ◽

Author(s):

Susanne Soelch ◽

Nathalie Beaufort ◽

Daniela Loessner ◽

Matthias Kotzsch ◽

Ute Reuning ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Epithelial To Mesenchymal Transition ◽

Transforming Growth Factor ◽

Cancer Cell Line ◽

Underlying Mechanism ◽

Mrna Levels ◽

Down Regulation ◽

Mesenchymal Transition

Abstract Background The small GTP-binding protein Rab31 plays an important role in the modulation of tumor biological-relevant processes, including cell proliferation, adhesion, and invasion. As an underlying mechanism, Rab31 is presumed to act as a molecular switch between a more proliferative and an invasive phenotype. This prompted us to analyze whether Rab31 overexpression in breast cancer cells affects expression of genes involved in epithelial-to-mesenchymal transition (EMT)-like processes when compared to Rab31 low-expressing cells. Methods Commercially available profiler PCR arrays were applied to search for differentially expressed genes in Rab31 high- and low-expressing CAMA-1 breast cancer cells. Differential expression of selected candidate genes in response to Rab31 overexpression in CAMA-1 cells was validated by independent qPCR and protein assays. Results Gene expression profiling of key genes involved in EMT, or its reciprocal process MET, identified 9 genes being significantly up- or down-regulated in Rab31 overexpressing CAMA-1 cells, with the strongest effects seen for TGFB1, encoding TGF-ß1 (> 25-fold down-regulation in Rab31 overexpressing cells). Subsequent validation analyses by qPCR revealed a strong down-regulation of TGFB1 mRNA levels in response to increased Rab31 expression not only in CAMA-1 cells, but also in another breast cancer cell line, MDA-MB-231. Using ELISA and Western blot analysis, a considerable reduction of both intracellular and secreted TGF-ß1 antigen levels was determined in Rab31 overexpressing cells compared to vector control cells. Furthermore, reduced TGF-ß activity was observed upon Rab31 overexpression in CAMA-1 cells using a sensitive TGF-ß bioassay. Finally, the relationship between Rab31 expression and the TGF-ß axis was analyzed by another profiler PCR array focusing on genes involved in TGF-ß signaling. We found 12 out of 84 mRNAs significantly reduced and 7 mRNAs significantly increased upon Rab31 overexpression. Conclusions Our results demonstrate that Rab31 is a potent modulator of the expression of TGF-ß and other components of the TGF-ß signaling pathway in breast cancer cells.

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