Inducing Physical Changes of Cancer Cells By Facilitating K+ Efflux of Big Potassium (BK) Channels; New Potential Target Genes in Cancer Metastasi Research
Session Number
MEDH 47
Advisor(s)
Ekrem Emrah Er, Ph.D, University of Illinois at Chicago
Discipline
Medical and Health Sciences
Start Date
17-4-2024 10:45 AM
End Date
17-4-2024 11:00 AM
Abstract
Changes in the physical characteristics of cancer cells are a hallmark of tumorigenesis, and understanding how these changes affect tumor progression can provide novel therapeutic insights. Prior studies have discovered that increasing cancer cell stiffness reduces metastatic burden by activating cytotoxic T lymphocytes. MRTFA and MRTFB are two transcription factors that cause the stiffening of cancer cells, and preliminary data demonstrates that MRTFA expression causes the expression of potassium (K+) handling genes like the auxiliary unit of the Big K+ (BK) channels, suggesting that these channels are downstream genes of MRTFA/B. We hypothesize that activating BK channels will stiffen cancer cells and enhance the ability of cytotoxic lymphocytes to detect and eliminate metastatic colonies via mechanosurvillence. To investigate the impact of agonists NS-11021 and BMS-20432 on the potency of NK cells, we performed and analyzed time-lapse imaging of the interaction of NK cells isolated from mouse spleens and mouse mammary tumor cells that were plated and treated with varying concentrations of KCl, NS-11021, and BMS-20432. Using PrismGraphpad to analyze twenty cells per condition, we concluded that there are no significant statistical differences in the time it takes to kill across the different KCl and agonistic-mediated conditions. In the future, we plan to increase cell count to increase statistical confidence. Nonetheless, we will continue investigating downstream genes of MRTFA/B to discover new avenues to target to potentially facilitate cell stiffening, triggering mechanosurveillance and thus hindering cancer metastasis and outgrowth.
Inducing Physical Changes of Cancer Cells By Facilitating K+ Efflux of Big Potassium (BK) Channels; New Potential Target Genes in Cancer Metastasi Research
Changes in the physical characteristics of cancer cells are a hallmark of tumorigenesis, and understanding how these changes affect tumor progression can provide novel therapeutic insights. Prior studies have discovered that increasing cancer cell stiffness reduces metastatic burden by activating cytotoxic T lymphocytes. MRTFA and MRTFB are two transcription factors that cause the stiffening of cancer cells, and preliminary data demonstrates that MRTFA expression causes the expression of potassium (K+) handling genes like the auxiliary unit of the Big K+ (BK) channels, suggesting that these channels are downstream genes of MRTFA/B. We hypothesize that activating BK channels will stiffen cancer cells and enhance the ability of cytotoxic lymphocytes to detect and eliminate metastatic colonies via mechanosurvillence. To investigate the impact of agonists NS-11021 and BMS-20432 on the potency of NK cells, we performed and analyzed time-lapse imaging of the interaction of NK cells isolated from mouse spleens and mouse mammary tumor cells that were plated and treated with varying concentrations of KCl, NS-11021, and BMS-20432. Using PrismGraphpad to analyze twenty cells per condition, we concluded that there are no significant statistical differences in the time it takes to kill across the different KCl and agonistic-mediated conditions. In the future, we plan to increase cell count to increase statistical confidence. Nonetheless, we will continue investigating downstream genes of MRTFA/B to discover new avenues to target to potentially facilitate cell stiffening, triggering mechanosurveillance and thus hindering cancer metastasis and outgrowth.