Evidence of BK_Ca Channelopathy-Driven Breast Cancer Metastasis to Brain

Abstract

KCNMA1 encodes the a-subunit of the large conductance, voltage and Ca 2+activated and Voltage-dependent potassium channel (BK Ca ) and was shown by others and us to be a potential drug target gene in several cancers, including breast cancer. In addition, we studied the role of alternative pre-mRNA splicing events of KCNMA1 in migration, invasion, proliferation and dispersal of breast cancer cells. It is conceivable that by targeting gene variants we can attenuate processes such as distant metastasis and angiogenesis. Here we reviewed literature on the alternative splicing events specific to breast cancer metastasis to brain, its microenvironment, the biological activity of most alternatively spliced isoforms. We conclude that based on our and others' work KCNMA1 and other such gene variants contribute to breast cancer dispersion, invasion, growth, and progression in the tumor microenvironment. Thus KCNMA1/BK Ca channels and their variants are opportunistic diagnostic, prognostic and treatment targets in breast cancer.