Expression and Role of the Intermediate-Conductance Calcium-Activated Potassium Channel KCa3.1 in Glioblastoma

Catacuzzeno, Luigi; Fioretti, Bernard; Franciolini, Fabio

doi:10.1155/2012/421564

Cited by 52 publications

(59 citation statements)

References 120 publications

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“…Consistent with previous observations [2], the activity of IK Ca channels was clearly detected in 13-06-MG cells. The probability of IK Ca -channel openings in these cells can be decreased by TRAM-34 or clotrimazole and be subject to stimulation by DCEBIO.…”

Section: Discussionsupporting

confidence: 92%

“…5A, in cell-attached patches, the activity of IK Ca channels with spontaneous open and closed transition was readily detected when the cell was held at -80 mV relative to the bath. Under our experimental conditions, the activity of IK Ca channels can be functionally expressed as reported previously in different types of cells [2,4,[13][14][15]. In cell-attached configuration, immediately following addition of 2 mM CaCl 2 or 10 µM ionomycin, IK Ca channels greatly opened with no change in single-channel amplitude.…”

Section: Properties Of Ik Ca Channels In 13-06-mg Cellsmentioning

confidence: 66%

“…Ion currents inherent in malignant glioma cells have been increasingly reported to influence the behavior of these cells [2][3][4][5][6][7][8][9][10]. Specifically, numerous reports demonstrated that any perturbations of functional expression in intermediate-conductance Ca 2+ -activated K + (IK Ca ) channels enriched in glioma cells or other types of neoplastic cells are capable of interfering with invasiveness or progression of malignant tumors [4,5,[11][12][13][14][15][16].…”

Section: Introductionmentioning

confidence: 99%

“…More importantly, the pharmacological modulators of IK Ca (K Ca 3.1) channels may represent an attractive therapeutic approach to a variety of tumors including gliomas [2,4,9,15,22]. However, whether OXAL or other related drugs exert any effects on the activity of IK Ca channels is not thoroughly understood, despite the fact that it can block K + currents [23].…”

Section: Introductionmentioning

confidence: 99%

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The Inhibition by Oxaliplatin, a Platinum-Based Anti-Neoplastic Agent, of the Activity of Intermediate-Conductance Ca2+-Activated K+ Channels in Human Glioma Cells

Huang

2015

Cell Physiol Biochem

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Oxaliplatin (OXAL) is a third-generation organoplatinum which is effective against advanced cancer cells including glioma cells. How this agent and other related compounds interacts with ion channels in glioma cells is poorly understood. OXAL (100 µM) suppressed the amplitude of whole-cell K⁺ currents (I_K); and, either DCEBIO or ionomycin significantly reversed OXAL-mediated inhibition of I_K in human 13-06-MG glioma cells. In OXAL-treated cells, TRAM-34 did not suppress I_K amplitude in these cells. The intermediate-conductance Ca²⁺-activated K⁺ (IK_Ca) channels subject to activation by DCEBIO and to inhibition by TRAM-34 or clotrimazole were functionally expressed in these cells. Unlike cisplatin, OXAL decreased the probability of IK_Ca-channel openings in a concentration-dependent manner with an IC₅₀ value of 67 µM. No significant change in single-channel conductance of IK_Ca channels in the presence of OXAL was demonstrated. Neither large-conductance Ca²⁺-activated K⁺ channels nor inwardly rectifying K⁺ currents in these cells were affected in the presence of OXAL. OXAL also suppressed the proliferation and migration of 13-06-MG cells in a concentration- and time-dependent manner. OXAL reduced IK_Ca-channel activity in LoVo colorectal cancer cells. Taken together, the inhibition by OXAL of IK_Ca channels would conceivably be an important mechanism through which it acts on the functional activities of glioma cells occurring in vivo.

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Section: Discussionsupporting

confidence: 92%

Section: Properties Of Ik Ca Channels In 13-06-mg Cellsmentioning

confidence: 66%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The Inhibition by Oxaliplatin, a Platinum-Based Anti-Neoplastic Agent, of the Activity of Intermediate-Conductance Ca2+-Activated K+ Channels in Human Glioma Cells

Huang

2015

Cell Physiol Biochem

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“…As a matter of fact, IK channels have been demonstrated to be indispensable for glioblastoma cell migration (for review, see ref. 9). Accordingly, IK protein expression in the tumor significantly correlates with poor survival of the patients with glioma (10).…”

Section: Introductionmentioning

confidence: 99%

Ca2+-Activated IK K+ Channel Blockade Radiosensitizes Glioblastoma Cells

Stegen

Butz

Klumpp

et al. 2015

Molecular Cancer Research

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Ca 2þ -activated K þ channels, such as BK and IK channels, have been proposed to fulfill pivotal functions in neoplastic transformation, malignant progression, and brain infiltration of glioblastoma cells. Here, the ionizing radiation (IR) effect of IK K þ channel targeting was tested in human glioblastoma cells. IK channels were inhibited pharmacologically by TRAM-34 or genetically by knockdown, cells were irradiated with 6 MV photons and IK channel activity, Ca 2þ signaling, cell cycling, residual doublestrand breaks, and clonogenic survival were determined. In addition, the radiosensitizing effect of TRAM-34 was analyzed in vivo in ectopic tumors. Moreover, The Cancer Genome Atlas (TCGA) was queried to expose the dependence of IK mRNA abundance on overall survival (OS) of patients with glioma. Results indicate that radiation increased the activity of IK channels, modified Ca 2þ signaling, and induced a G 2 -M cell-cycle arrest. TRAM-34 decreased the IR-induced accumulation in G 2 -M arrest and increased the number of gH2AX foci post-IR, suggesting that TRAM-34 mediated an increase of residual DNA double-strand breaks. Mechanistically, IK knockdown abolished the TRAM-34 effects indicating the IK specificity of TRAM-34. Finally, TRAM-34 radiosensitized ectopic glioblastoma in vivo and high IK mRNA abundance associated with shorter patient OS in low-grade glioma and glioblastoma.Implications: Together, these data support a cell-cycle regulatory function for IK K þ channels, and combined therapy using IK channel targeting and radiation is a new strategy for anti-glioblastoma therapy. Mol Cancer Res; 13(9); 1283-95. Ó2015 AACR.

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The potassium channel KCa3.1 promotes cell proliferation by activating SKP2 and metastasis through the EMT pathway in hepatocellular carcinoma

Song

Chen

et al. 2019

Intl Journal of Cancer

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The intermediate conductance calcium‐activated potassium channel (KCa3.1) plays an important role in maintaining intracellular calcium homeostasis and is involved in the tumorigenesis of many human cancers. However, it is unknown whether KCa3.1 plays a role in the genesis of hepatocellular carcinoma (HCC), one of the most common malignant tumors worldwide with a very poor prognosis. In our study, we found that the expression of KCa3.1 was significantly elevated in poorly differentiated HCC tissues compared to adjacent noncancerous tissues. In vitro and in vivo experiments showed that KCa3.1 could promote cell proliferation, migration, and invasion of HCC. Mechanistically, KCa3.1 promoted cell cycle progression and migration and invasion of HCC cells by activating S‐phase protein kinase 2 (SKP2) to trigger the degradation of p21 and p27 and targeting Reelin (RELN) to induce epithelial‐mesenchymal transition (EMT), respectively. Taken together, our results demonstrate that KCa3.1 plays an important role in the genesis and progression of HCC, implying that it might be a promising therapeutic target in HCC.

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Expression and Role of the Intermediate-Conductance Calcium-Activated Potassium Channel KCa3.1 in Glioblastoma

Cited by 52 publications

References 120 publications

The Inhibition by Oxaliplatin, a Platinum-Based Anti-Neoplastic Agent, of the Activity of Intermediate-Conductance Ca2+-Activated K+ Channels in Human Glioma Cells

The Inhibition by Oxaliplatin, a Platinum-Based Anti-Neoplastic Agent, of the Activity of Intermediate-Conductance Ca2+-Activated K+ Channels in Human Glioma Cells

Ca2+-Activated IK K+ Channel Blockade Radiosensitizes Glioblastoma Cells

The potassium channel KCa3.1 promotes cell proliferation by activating SKP2 and metastasis through the EMT pathway in hepatocellular carcinoma

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