Effect of Kv11.1 Potassium Ion Channel Activator NS1643 on the Metastatic Potential of Triple Negative Breast Cancer Cells

Triple-Negative Breast Cancer (TNBC) is an aggressive subtype characterized by high metastatic potential and limited treatment options. Previous research done in the Minshall Lab suggests that the Kv11.1 K⁺ channel activator NS1643 reduces TNBC metastasis in part by enhancing β-catenin interaction with desmosomal proteins, thereby strengthening cell-cell and cell-matrix adhesion. Building on these findings, we investigated the impact of NS1643 on TNBC cell motility by tracking cellular movement at varying concentrations (5 μM, 10 μM, 25 μM, and 50 μM). Using live-cell imaging and computational analysis, we observed a dose- dependent decrease in cellular velocity. At 50 μM NS1643, TNBC cells exhibited minimal motility, suggesting a significant reduction in metastatic potential. This aligns with our prior findings that NS1643 promotes the formation of desmosomes/hemidesmosomes, reinforcing intercellular adhesion. These results highlight the potential of NS1643 as an anti-metastatic agent by both enhancing cellular adhesion and reducing migration. Further studies will explore the molecular mechanisms underlying this phenomenon, particularly its impact on cytoskeletal dynamics and signaling pathways. Thus, this study is beginning to reveal a potentially promising pharmacological mechanism for inhibiting breast cancer metastasis by increasing desmosome adhesions.