Identification of SK3 channel as a new mediator of breast cancer cell migration

Abstract

Potassium channels have been involved in epithelial tumorigenesis but the role of small-conductance Ca 2+ -activated K + channels is unknown. We report here that small-conductance Ca 2+ -activated K + channels are expressed in a highly metastasizing mammary cancer cell line, MDA-MB-435s. Patch-clamp recordings showed typical small-conductance Ca 2+ -activated K + channelmediated currents sensitive to apamin, 4-aminopyridine, and tetraethylammonium. Moreover, the cells displayed a high intracellular calcium concentration, which was decreased after 24 hours of apamin treatment. By regulating membrane potential and intracellular calcium concentration, these channels were involved in MDA-MB435s cell migration, but not in proliferation. Only SK3 protein expression was observed in these cells in contrast to SK2, which was expressed both in cancer and noncancer cell lines. Whereas small interfering RNA directed against SK3 almost totally abolished MDA-MB435s cell migration, transient expression of SK3 increased migration of the SK3-deficient cell lines, MCF-7 and 184A1. SK3 channel was solely expressed in tumor breast biopsies and not in nontumor breast tissues. Thus, SK3 protein channel seems to be a new mediator of breast cancer cell migration and represents a potential target for a new class of anticancer agents.

Ion Channels as Promising Therapeutic Targets for Melanoma

“…Among SKCa channels, SK3 channel was found to promote breast and colon epithelial cancer cells and, melanoma cells migration by hyperpolarizing plasma cell membrane (Chantôme et al, 2009;Potier et al, 2006;Potier et al, 2010). As mentioned above, SK3 protein is produced in melanoma cells but not in untransformed melanocytes (Chantôme et al, 2009).…”

“…2). Indeed, an increase of K + efflux shifts the membrane potential towards negative values (hyperpolarization) and consequently increases the Ca 2+ driving force (Potier et al, 2006;Rao et al, 2006;Rao et al, 2002). Inversely, a reduction of SK3 channel activity may depolarize the plasma membrane and reduce Ca 2+ entry.…”

Physiologie, pharmacologie et modélisation de canaux potassiques

“…Plus récemment, un composé d'une autre classe également accroître l'excitabilité des neurones dopaminergiques de la substance noire, ce qui pourrait être utile dans le traitement de certaines maladies liées à un dysfonctionnement de ces systèmes [1,24]. Des études plus récentes ont également présenté les canaux SK comme cibles potentielles dans d'autres pathologies sévères telles que le cancer du sein [4], la fibrillation auriculaire [25] ou encore les désordres cognitifs liés à la schizophrénie [26]. Ce large éventail de possibilités thérapeutiques justifie l'étude d'une telle cible.…”

“…Chez l'homme, les canaux K + sont impliqués dans divers processus physiologiques tels que la libération synaptique de neurotransmetteurs dont les fluctuations sous-tendent les phénomènes de mémorisation, la contraction musculaire, et la régulation du rythme cardiaque [1,2]. Dans les cellules non excitables, les canaux K + sont impliqués dans le contrôle du volume cellulaire, la prolifération, l'apoptose, ou encore la migration cellulaire [1][2][3][4][5].…”

Copy number variation in archival melanoma biopsies versus benign melanocytic lesions

“…185 Patients ranged in age from 14 to 90 years (Table 1). 186 The cohort of biopsy specimens used in this study was 187 collected between 2001 and 2013, making their age 188 range between 2 and 14 years.…”