Electric Fields Control Motility of Metastatic Breast Cancer Cells

By: Ayush Garg

The onset of metastasis in breast cancer patients reduces their survival rates from over 90% to less than 20%. The key to stopping and treating metastatic breast lesions lies in understanding the mechanisms that regulate cancer cell migration. Mechanisms that regulate cancer cell migration in response to chemical cues, mechanical cues, physical cues etc. have been widely studied but effects of electric fields on motility are not well understood. While previous direct current electric field (dc EF) studies have shown directional galvanotactic migratory response in various cancer cells, the underlying mechanisms regulating this responses are still unclear. Here we show that by applying non-contact induced electric fields (iEFs, field strength < 100 µV/cm), we can directionally increase spontaneous migration rate of MDA-MB-231 cells. We found that this directional response was Akt dependent. Further, iEFs directionally hindered epidermal growth factor (EGF) induced migration of MDA-MB-231s by inhibiting EGFR phosphorylation, adversely impacting normal mitochondrial function, and disrupting actin polarization. Finally, we found that combined treatment of iEFs with MK2206 (an Akt inhibitor), resulted in ~21% slower migration speeds compared to untreated controls. Taken collectively, this body of results represents a significant step toward identifying how low frequency (< 1 MHz) iEFs interact with mammalian breast cancer cells and the possible governing mechanisms controlling their migratory responses. The results presented here could lay the foundation for exploring non-contact and new therapeutic approaches that may be used in a stand-alone manner or in conjunction with chemotherapy such as an Akt inhibitor based strategy.