KCa2.3 channel-dependent hyperpolarization increases melanoma cell motility

Chantôme, Aurélie; Girault, Alban; Potier, Marie‐Claude; Collin, Christine; Vaudin, Pascal; Pagès, Jean‐Christophe; Vandier, Christophe; Joulin, Virginie

doi:10.1016/j.yexcr.2009.07.021

Cited by 68 publications

(90 citation statements)

References 40 publications

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“…Involvement of theses channels have been investigated in melanoma cells because their resulting K + efflux could provide a membrane hyperpolarisation necessary to cell proliferation. In agreement with the reported restricted expression pattern of SK1 channel mainly found in neuronal tissues, transcript was no detected in melanoma cells and in normal human epidermal melanocytes NHEM (Chantôme et al, 2009;Tajima et al, 2006). In contrast, SK2 transcripts were always detected in melanocyte and melanoma cell lines but electrophysiological analyses revealed that SK2 channels were not functional in the three melanoma cell lines tested (IGR-1, SKmel-28 and 518A2) (Chantôme et al, 2009;Meyer et al, 1999;Tajima et al, 2006).…”

Section: Small and Intermediate Calcium-activated Potassium Channel (supporting

confidence: 88%

“…In agreement with the reported restricted expression pattern of SK1 channel mainly found in neuronal tissues, transcript was no detected in melanoma cells and in normal human epidermal melanocytes NHEM (Chantôme et al, 2009;Tajima et al, 2006). In contrast, SK2 transcripts were always detected in melanocyte and melanoma cell lines but electrophysiological analyses revealed that SK2 channels were not functional in the three melanoma cell lines tested (IGR-1, SKmel-28 and 518A2) (Chantôme et al, 2009;Meyer et al, 1999;Tajima et al, 2006). Interestingly, SK2 transcripts level and KCa (SK2 et KCa3.1) currents are increase under hypoxia and only in this condition, apamin application, a non specific pore blocker of SK2, reduced cell proliferation rates in IGR-1 melanoma cells (Tajima et al, 2006).…”

Section: Small and Intermediate Calcium-activated Potassium Channel (supporting

confidence: 88%

“…Interestingly, SK2 transcripts level and KCa (SK2 et KCa3.1) currents are increase under hypoxia and only in this condition, apamin application, a non specific pore blocker of SK2, reduced cell proliferation rates in IGR-1 melanoma cells (Tajima et al, 2006). SK3 transcripts and functional SK3 channels have been found in several melanoma cells but not in untransformed melanocytes (Chantôme et al, 2009;Tajima et al, 2006). It has been clearly demonstrated that SK3-dependent efflux regulates membrane potential in 518A2 and SKmel-28 melanoma cells (Chantôme et al, 2009).…”

Section: Small and Intermediate Calcium-activated Potassium Channel (mentioning

confidence: 98%

See 2 more Smart Citations

Ion Channels as Promising Therapeutic Targets for Melanoma

Chantôme¹,

Potier-Cartereau²,

Roger³

et al. 2011

Breakthroughs in Melanoma Research

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Section: Small and Intermediate Calcium-activated Potassium Channel (supporting

confidence: 88%

Section: Small and Intermediate Calcium-activated Potassium Channel (supporting

confidence: 88%

Section: Small and Intermediate Calcium-activated Potassium Channel (mentioning

confidence: 98%

See 1 more Smart Citation

Ion Channels as Promising Therapeutic Targets for Melanoma

Chantôme¹,

Potier-Cartereau²,

Roger³

et al. 2011

Breakthroughs in Melanoma Research

Self Cite

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“…In cells transfected with siP2X 7 , ATP was not able to increase cell migration ( Figure 4b). Recently, it has been shown that SK3 channels, from the family of small-conductance Ca 2 þ -activated potassium channels (SK Ca ), were important regulators of breast , colon (Potier et al, 2010) and melanoma (Chantome et al, 2009) cancer cells migration. We first verified that siRNA directed against mRNA for P2X 7 R did not interfere with SK3 protein expression (supplementary Figure 2B).…”

Section: Human Cancer Cells Express Functional P2x 7 Rmentioning

confidence: 99%

“…To inhibit SK3 channel expression, we constructed a lentiviral vector encoding a short hairpin RNA (shRNA) specifically targeting the human KCa2.3 gene as using the same protocol than already reported, but adapted to breast cancer cells (Chantome et al, 2009). Briefly, the sequence encoding shSK3 was obtained by PCR elongation of two partially complementary primers; this also allowed us to introduce two restriction enzyme sites to facilitate manipulations.…”

Section: Cells and Culturementioning

confidence: 99%

P2X7 receptor activation enhances SK3 channels- and cystein cathepsin-dependent cancer cells invasiveness

et al. 2011

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ATP-gated P2X 7 receptors (P2X 7 R) are unusual plasma membrane ion channels that have been extensively studied in immune cells. More recently, P2X 7 R have been described as potential cancer cell biomarkers. However, mechanistic links between P2X 7 R and cancer cell processes are unknown. Here, we show, in the highly aggressive human breast cancer cell line MDA-MB-435s, that P2X 7 receptor is highly expressed and fully functional. Its activation is responsible for the extension of neurite-like cellular prolongations, of the increase in cell migration by 35% and in cell invasion through extracellular matrix by 150%. The change in cancer cell morphology and the increased migration appeared to be due to the activation of Ca 2 þ -activated SK3 potassium channels. The enhanced invasion through the extracellular matrix was related to the increase of mature forms of cysteine cathepsins in the extracellular medium, which was independent of SK3 channel activity and not associated with cell death. Pharmacological targeting of P2X 7 R in vivo was crucial for cell invasiveness in a zebrafish model of metastases. Our results demonstrate a novel mechanistic link between P2X 7 R functionality in cancer cells and invasiveness, a key parameter in tumour growth and in the development of metastases. They also suggest a potential therapeutic role for the newly developed P2X 7 R antagonists.

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New Disaccharide‐Based Ether Lipids as SK3 Ion Channel Inhibitors

et al. 2016

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The SK3 potassium channel is involved in the development of bone metastasis and in the settlement of cancer cells in Ca(2+) -rich environments. Ohmline, which is a lactose-based glycero-ether lipid, is a lead compound that decreases SK3 channel activity and consequently limits the migration of SK3-expressing cells. Herein we report the synthesis of three new ohmline analogues in which the connection of the disaccharide moieties (1→6 versus 1→4) and the stereochemistry of the glycosyl linkage was studied. Compound 2 [3-(hexadecyloxy)-2-methoxypropyl-6-O-α-d-glucopyranosyl-β-d-galactopyranoside], which possesses an α-glucopyranosyl-(1→6)-β-galactopyranosyl moiety, was found to decrease SK3 current amplitude (70 % inhibition at 10 μm), displace SK3 protein outside caveolae, and decrease constitutive Ca(2+) entry (50 % inhibition at 300 nm) and SK3-dependent cell migration (30 % at 300 nm) at a level close to that of the benchmark compound ohmline. Compound 2, which decreases the activity of SK3 channel (but not SK2 channel), is a new drug candidate to reduce cancer cell migration and to prevent bone metastasis.

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KCa2.3 channel-dependent hyperpolarization increases melanoma cell motility

Cited by 68 publications

References 40 publications

Ion Channels as Promising Therapeutic Targets for Melanoma

Ion Channels as Promising Therapeutic Targets for Melanoma

P2X7 receptor activation enhances SK3 channels- and cystein cathepsin-dependent cancer cells invasiveness

New Disaccharide‐Based Ether Lipids as SK3 Ion Channel Inhibitors

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