Potassium channels in cell cycle and cell proliferation

Abstract

Normal cell-cycle progression is a crucial task for every multicellular organism, as it determines body size and shape, tissue renewal and senescence, and is also crucial for reproduction. On the other hand, dysregulation of the cell-cycle progression leading to uncontrolled cell proliferation is the hallmark of cancer. Therefore, it is not surprising that it is a tightly regulated process, with multifaceted and very complex control mechanisms. It is now well established that one of those mechanisms relies on ion channels, and in many cases specifically on potassium channels. Here, we summarize the possible mechanisms underlying the importance of potassium channels in cell-cycle control and briefly review some of the identified channels that illustrate the multiple ways in which this group of proteins can influence cell proliferation and modulate cell-cycle progression.

IK1-enhanced human-induced pluripotent stem cell-derived cardiomyocytes: an improved cardiomyocyte model to investigate inherited arrhythmia syndromes

“…Kir2.1 membrane hyperpolarization was shown by this same group to trigger the calcineurin pathway, which in turn activates myogenic transcription factors, myogenin and myocyte enhancer factor-2, and initiates essential steps involved in differentiation and maturation of skeletal muscle (10). Potassium channels may regulate cell size and volume by permeation-dependent mechanisms and cellular hyperpolarization and possibly via modulation of signaling cascades by protein-protein interactions as reviewed by Urrego et al (27). Our I K1 -enhanced iPS-CMs showed a nearly twofold increase in cell capacitance values compared with previous reports for iPS-CMs (18).…”

Ion channels in cancer: future perspectives and clinical potential

“…K þ channels participate in the machinery regulating cell cycle [110,111]. K þ channels may affect proliferation further by altering cell volume [5].…”

Targeting potassium channels in cancer

“…So it is important to determine whether overexpression of a specific potassium channel in situ of an animal model is tumorigenic, which is a more stringent criterion for an oncogene. Considering the fact that pharmacological inhibition or genetic suppression of potassium channels reduces growth in multiple cancer types Urrego et al, 2014), it is possible that most potassium channels take up a "permissive" role to mostly function as essential regulators for various cancer cell behaviors such as proliferation and migration, and that their up-regulation provides a repertoire for sufficient channel activity when necessary. Strikingly, up-regulation of the plant orthologue of Shaker-like voltage-gated potassium channel AKT1 has been detected in Arabidopsis thaliana tumors induced by bacterial infection, and the plant tumor growth is reduced in AKT1 channel mutants (Deeken et al, 2003), highlighting the evolutionarily conserved mechanism for potassium channels to drive tumor growth.…”