Cancer-Associated Intermediate Conductance Ca2+-Activated K+ Channel KCa3.1

Abstract

Several tumor entities have been reported to overexpress KCa3.1 potassium channels due to epigenetic, transcriptional, or post-translational modifications. By modulating membrane potential, cell volume, or Ca2+ signaling, KCa3.1 has been proposed to exert pivotal oncogenic functions in tumorigenesis, malignant progression, metastasis, and therapy resistance. Moreover, KCa3.1 is expressed by tumor-promoting stroma cells such as fibroblasts and the tumor vasculature suggesting a role of KCa3.1 in the adaptation of the tumor microenvironment. Combined, this features KCa3.1 as a candidate target for innovative anti-cancer therapy. However, immune cells also express KCa3.1 thereby contributing to T cell activation. Thus, any strategy targeting KCa3.1 in anti-cancer therapy may also modulate anti-tumor immune activity and/or immunosuppression. The present review article highlights the potential of KCa3.1 as an anti-tumor target providing an overview of the current knowledge on its function in tumor pathogenesis with emphasis on vasculo- and angiogenesis as well as anti-cancer immune responses.

Keywords

• KCa3.1
• intermediate conductance calcium-activated K+ channel
• BK
• big conductance Ca2+- and voltage-activated K+ channels
• TRAM-34
• (1-[(2-chlorophenyl) diphenylmethyl]-pyrazole
• 1-EBIO
• 1-Ethyl-1,3-dihydro-2H-benzimidazol-2-one
• E2
• 17-estradiol