Effect of Kv11.1 K+ channel activator NS1643 on Desmoplakin and Plankophilin Expression and Localization in Triple Negative Breast Cancer Cells
Session Number
MEDH 55
Advisor(s)
Dr. Richard D. Minshall, University of Illinois at Chicago, Departments of Pharmacology and Anesthesiology
Discipline
Medical and Health Sciences
Start Date
17-4-2025 10:45 AM
End Date
17-4-2025 11:00 AM
Abstract
African American and Hispanic women world-wide are more likely to exhibit a worse outcome from triple negative breast cancer (TBNC), which is why new therapeutics are desperately needed. Interestingly, their cells uniquely overexpress the potassium ion channel, Kv11.1, which affects mechanisms regulating cell proliferation and metastasis. A study by the Minshall lab showed that a drug called NS1643 activates Kv11.1 and reduces cell migration and enhanced interaction of β-Catenin with Adherens Junctions, Focal Adhesions, and Desmosomal Proteins. They showed that activation of Kv11.1 with the drug promoted dephosphorylation of Caveolin-1, a signal regular, resulting in β-catenin disassociation from Cav-1. Our evolving hypothesis is that NS1643-induced Cav-1 dephosphorylation in TNBC cells promotes the formation of cell-cell and cell-matrix adhesions dependent on β-catenin. We have analyzed cell movement and expression of both desmoplakin and plakophilin in TNBC cells by using ImageJ software. To further understand the impact of this drug, we conducted a TEER to assess the expression of Desmoplakin and Plakophilin in TNBCs treated with NS1643 and observed there was no effect on the expression for the two proteins after using the drug. Ongoing experiments will determine if this effect is dependent on βcatenin. NS1643 has promise in protecting women in the future
Effect of Kv11.1 K+ channel activator NS1643 on Desmoplakin and Plankophilin Expression and Localization in Triple Negative Breast Cancer Cells
African American and Hispanic women world-wide are more likely to exhibit a worse outcome from triple negative breast cancer (TBNC), which is why new therapeutics are desperately needed. Interestingly, their cells uniquely overexpress the potassium ion channel, Kv11.1, which affects mechanisms regulating cell proliferation and metastasis. A study by the Minshall lab showed that a drug called NS1643 activates Kv11.1 and reduces cell migration and enhanced interaction of β-Catenin with Adherens Junctions, Focal Adhesions, and Desmosomal Proteins. They showed that activation of Kv11.1 with the drug promoted dephosphorylation of Caveolin-1, a signal regular, resulting in β-catenin disassociation from Cav-1. Our evolving hypothesis is that NS1643-induced Cav-1 dephosphorylation in TNBC cells promotes the formation of cell-cell and cell-matrix adhesions dependent on β-catenin. We have analyzed cell movement and expression of both desmoplakin and plakophilin in TNBC cells by using ImageJ software. To further understand the impact of this drug, we conducted a TEER to assess the expression of Desmoplakin and Plakophilin in TNBCs treated with NS1643 and observed there was no effect on the expression for the two proteins after using the drug. Ongoing experiments will determine if this effect is dependent on βcatenin. NS1643 has promise in protecting women in the future