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

Several tumor entities have been reported to overexpress K(Ca)3.1 potassium channels due to epigenetic, transcriptional, or post-translational modifications. By modulating membrane potential, cell volume, or Ca2+ signaling, K(Ca)3.1 has been proposed to exert pivotal oncogenic functions in tumorigenesis, malignant progression, metastasis, and therapy resistance. Moreover, K(Ca)3.1 is expressed by tumor-promoting stroma cells such as fibroblasts and the tumor vasculature suggesting a role of K(Ca)3.1 in the adaptation of the tumor microenvironment. Combined, this features K(Ca)3.1 as a candidate target for innovative anti-cancer therapy. However, immune cells also express K(Ca)3.1 thereby contributing to T cell activation. Thus, any strategy targeting K(Ca)3.1 in anti-cancer therapy may also modulate anti-tumor immune activity and/or immunosuppression. The present review article highlights the potential of K(Ca)3.1 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.