Potassium and Calcium Channel Complexes as Novel Targets for Cancer Research

Abstract

The intracellular Ca²⁺ concentration is mainly controlled by Ca²⁺ channels. These channels form complexes with K⁺ channels, which function to amplify Ca²⁺ flux. In cancer cells, voltage-gated/voltage-dependent Ca²⁺ channels and non-voltage-gated/voltage-independent Ca²⁺ channels have been reported to interact with K⁺ channels such as Ca²⁺-activated K⁺ channels and voltage-gated K⁺ channels. These channels are activated by an increase in cytosolic Ca²⁺ concentration or by membrane depolarization, which induces membrane hyperpolarization, increasing the driving force for Ca²⁺ flux. These complexes, composed of K⁺ and Ca²⁺ channels, are regulated by several molecules including lipids (ether lipids and cholesterol), proteins (e.g. STIM), receptors (e.g. S1R/SIGMAR1), and peptides (e.g. LL-37) and can be targeted by monoclonal antibodies, making them novel targets for cancer research.

Keywords: Ca2+ channels; Cancer; K+ channels; LL-37; Lipids; SIGMAR1; STIM.