Ca²⁺-activated K⁺ channels as cancer therapeutic targets

Abstract

Similar to calcium (Ca²⁺) and chloride (Cl⁻) ion channels/transporters, potassium (K⁺) channels have been recognized as a crucial cancer treatment target. Recent studies have provided convincing evidences of positive correlation between elevated expression levels of Ca²⁺-activated K⁺ (K_Ca) channels and cancer proliferation, metastasis, and poor patient prognosis. In cancer cells, K_Ca1.1 and K_Ca3.1 K_Ca channels are co-localized with Ca²⁺-permeable Orai/TRP channels to provide a positive-feedback loop for Ca²⁺ entry. They are responsible for the promotion of cell growth and metastasis in the different types of cancer, and are therefore potential therapeutic targets and biomarkers for cancer. We determined the epigenetic and post-transcriptional dysregulation of K_Ca3.1 by class I histone deacetylase inhibitors in breast and prostate cancer cells. We further determined the transcriptional repression and protein degradation of K_Ca1.1 by vitamin D receptor agonists and androgen receptor antagonists, which are expected as potential therapeutic drugs for triple-negative breast cancer. The anti-inflammatory cytokine, interleukin-10 (IL-10) is an immunosuppressive factor involved in tumorigenesis, and plays a crucial role in escape from tumor immune surveillance. We determined K_Ca3.1 activators are a possible therapeutic option to suppress the tumor-promoting activities of IL-10. These results may provide new insights into cancer treatment focused on Ca²⁺-activated K⁺ channels.