Abstract 1757 Investigating the effect of WNK lysine deficient protein kinase inhibition in breast cancer

Breast Cancer (BCa) is the second leading cause of cancer-associated death in women in the United States and poses a significant health concern. Over the years, the progress made in screening, diagnosis and management of BCa have improved the clinical outcomes in patients. Nevertheless, the disease remains a significant threat to the wellness of women as almost all patients with advanced metastatic forms of the disease ultimately succumb to the disease. Thus, there is a critical need to identify new and novel signaling pathways and therapeutic strategies targeting those pathways to treat metastatic BCa. In this study we identified the role of with-no-lysine protein kinase 1 (WNK1), a serine threonine kinase primarily involved with blood pressure regulation, in BCa progression. WNK1, which is primarily expressed in BCa, shows a strong association with lover overall survival of BCa patients. However, its exact role in BCa is not clearly understood. Using and analyzing publicly available datasets and conducting IHC and Western Blot analyses, we observed strong WNK1 expression in BCa cells and fibroblasts, the most abundant cell types in the BCa microenvironment. Using murine BCa cells and mouse embryonic fibroblasts, we determined that inhibition of WNK1 using WNK1 inhibitors significantly inhibits the growth of cancer cells and fibroblasts. These results lead us to believe that WNK1 could be a potential therapeutic target in the treatment of BCa. Our findings are currently being confirmed in vivo where we are investigating the effects of WNK1 inhibition on tumor growth and progression. This study was supported by funds from the Mitchell Cancer Institute (MCI) and Breast Cancer Research Foundation of Alabama (BCRFA).