Letter to the Editor: “Ion Channels in Brain Metastasis”—Ion Channels in Cancer Set up and Metastatic Progression

D’Arcangelo, Daniela; Nicodemi, E; Facchiano, Antonio

doi:10.3390/ijms18040718

Cited by 1 publication

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“…The number of studies relating ion channels to melanoma has increased in the last few years and ion channels are now recognized as potential co-targets in the new melanoma therapeutic strategies currently under continuous development [43]. We have previously reported strong and significant expression changes of several ion channels in solid tumors including glioblastoma, breast cancer, lung cancer, bladder cancer, and melanoma [19] and also proposed a possible role of ion channels in brain metastases onset [44]. Figure 3 of the present study also underlines that several studies identify reciprocal stimulatory relationships of melanoma and ion channels.…”

Section: Discussionmentioning

confidence: 99%

Ion Channel Expression in Human Melanoma Samples: In Silico Identification and Experimental Validation of Molecular Targets

D’Arcangelo

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Giampietri

et al. 2019

Cancers

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Expression of 328 ion channel genes was investigated, by in silico analysis, in 170 human melanoma samples and controls. Ninety-one members of this gene-family (i.e., about 28%) show a significant (p < 0.05) differential expression in melanoma- vs. nevi-biopsies, taken from the GEO database. ROC (receiver operating characteristic) analysis selected 20 genes as potential markers showing the highest discrimination ability of melanoma vs. nevi (AUC > 0.90 and p < 0.0001). These 20 genes underwent a first in silico-validation round in an independent patients-dataset from GEO. A second-in silico-validation step was then carried out on a third human dataset in Oncomine. Finally, five genes were validated, showing extremely high sensitivity and specificity in melanoma detection (>90% in most cases). Such five genes (namely, SCNN1A, GJB3, KCNK7, GJB1, KCNN2) are novel potential melanoma markers or molecular targets, never previously related to melanoma. The “druggable genome” analysis was then carried out. Miconazole, an antifungal drug commonly used in clinics, is known to target KCNN2, the best candidate among the five identified genes. Miconazole was then tested in vitro in proliferation assays; it dose-dependently inhibited proliferation up to 90% and potently induced cell-death in A-375 and SKMEL-28 melanoma cells, while it showed no effect in control cells. Moreover, specific silencing of KCNN2 ion channel was achieved by siRNA transfection; under such condition miconazole strongly increases its anti-proliferative effect. In conclusion, the present study identified five ion channels that can potentially serve as sensitive and specific markers in human melanoma specimens and demonstrates that the antifungal drug miconazole, known to target one of the five identified ion channels, exerts strong and specific anti-melanoma effects in vitro.

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Section: Discussionmentioning

confidence: 99%

Ion Channel Expression in Human Melanoma Samples: In Silico Identification and Experimental Validation of Molecular Targets

D’Arcangelo

Scatozza

Giampietri

et al. 2019

Cancers

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Letter to the Editor: “Ion Channels in Brain Metastasis”—Ion Channels in Cancer Set up and Metastatic Progression

Abstract: The review by Klumpp, L. et al. entitled Ion Channels in Brain Metastasis [1] discusses the role of ion channels in breast cancer, lung cancer and melanoma in metastatic tropism to the brain [...]

Cited by 1 publication

References 9 publications

Ion Channel Expression in Human Melanoma Samples: In Silico Identification and Experimental Validation of Molecular Targets

Ion Channel Expression in Human Melanoma Samples: In Silico Identification and Experimental Validation of Molecular Targets

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