Intermediate-conductance Ca2+-activated K+ channels (IKCa1) regulate human prostate cancer cell proliferation through a close control of calcium entry

Abstract

Accumulating data point to K þ channels as relevant players in controlling cell cycle progression and proliferation of human cancer cells, including prostate cancer (PCa) cells. However, the mechanism(s) by which K þ channels control PCa cell proliferation remain illusive. In this study, using the techniques of molecular biology, biochemistry, electrophysiology and calcium imaging, we studied the expression and functionality of intermediate-conductance calcium-activated potassium channels (IK Ca1 ) in human PCa as well as their involvement in cell proliferation. We showed that IK Ca1 mRNA and protein were preferentially expressed in human PCa tissues, and inhibition of the IK Ca1 potassium channel suppressed PCa cell proliferation. The activation of IK Ca1 hyperpolarizes membrane potential and, by promoting the driving force for calcium, induces calcium entry through TRPV6, a cation channel of the TRP (Transient Receptor Potential) family. Thus, the overexpression of the IK Ca1 channel is likely to promote carcinogenesis in human prostate tissue.

Migration-associated secretion of melanoma inhibitory activity at the cell rear is supported by KCa3.1 potassium channels

“…A migratory stimulus leads to elevation in intracellular Ca 2+ concentration, which activates the KCa3.1 channel. The channel activity in turn causes hyperpolarization of the cell membrane and thus a higher electrochemical driving force for Ca 2+ influx [21,68]. Consequently, we found that channel inhibition reduced the intracellular Ca 2+ levels, while expression of KCa3.1 leads to elevated Ca 2+ levels in transfected cells.…”

“…Another player linking intracellular Ca 2+ ions and cell migration is the calcium-activated potassium channel KCa3.1. This channel type was found to be aberrantly expressed in various tumor types and implicated in the promotion of cell migration and cell proliferation [18][19][20][21]. In migrating cells, KCa3.1 channel activity was detected predominantly at the rear cell pole [22], which may be due to the intracellular Ca 2+ gradient in polarized, migrating cells.…”

SK4 channels modulate Ca2+ signalling and cell cycle progression in murine breast cancer

“…Aberrant K + efflux via oncogenic K Ca channels may affect multiple parameters in the breast tumour cell such as membrane potential, cytosolic Ca 2+ ([Ca 2+ ] i ), pH and cell volume (Huang and Jan, 2014; Huber, 2013). Current knowledge suggests that BK (Lallet‐Daher et al ., 2009; Parihar et al ., 2003; Stegen et al ., 2015) and SK4 (Ouadid‐Ahidouch et al ., 2004; Parihar et al ., 2003; Steinle et al ., 2011) activities are required for malignant growth of several tumour‐derived cell lines and of xenografts in immunocompromised mice, highlighting a general role of K Ca channels for cell cycle‐specific functions (Huang and Jan, 2014; Pardo and Stuhmer, 2014). Expression of SK4 and BK in cancer cells follows a cell cycle‐dependent mode (Ouadid‐Ahidouch et al ., 2004; Pardo et al ., 1998) and the mitogen‐dependent regulation of K Ca activity supports a role for both channels in malignant (Faouzi et al ., 2010; Lallet‐Daher et al ., 2009; Wang et al ., 2007a) and nonmalignant cell proliferation (Grgic et al ., 2005; Khanna et al ., 1999; Toyama et al ., 2008; Yu et al ., 2013).…”

Calcium and Vitamin D Supplementation During Androgen Deprivation Therapy for Prostate Cancer: A Critical Review

“…However, a potential mechanism involves the effects of dietary calcium increasing the level of ionized calcium in blood [82,83]. Prostate cancer cells express both the calcium-sensing receptor [84] and calcium-dependent voltage-gated channels [85]. Stimulation of these receptors by extracellular calcium increases prostate cancer cell growth in vitro and in vivo.…”