Membrane Transporters and Channels in Melanoma

Böhme, Ines; Schönherr, Roland; Eberle, Jürgen; Boßerhoff, Anja

doi:10.1007/112_2020_17

Cited by 12 publications

(9 citation statements)

References 324 publications

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“…ASIC5 was found to be activated in the ethanol-(100 mM)-exposed neonatal rat cardiomyocytes along with other six molecules (CYP2A6, PRL, CHRNA4, CNR1, CRH, and SLC40A1) (56). Low (in 50%) ASIC5 protein expression in melanoma were observed with <4% mutation rates (57).…”

Section: Discussionmentioning

confidence: 96%

Whole-Genome Sequencing Reveals Exonic Variation of ASIC5 Gene Results in Recurrent Pregnancy Loss

et al. 2021

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Family trio next-generation sequencing-based variant analysis was done to identify the genomic reason on unexplained recurrent pregnancy loss (RPL). A family (dead fetus and parents) from Saudi Arabia with an earlier history of three unexplained RPLs at the ninth week of pregnancy was included in the study. Whole-genome sequencing (WGS) of a dead fetus and the parents was done to identify the pathogenic variation and confirmed through Sanger sequencing. WGS of dead fetus identifies a novel homozygous exonic variation (NM_017419.3:c.680G>T) in ASIC5 (acid-sensing ion channel subunit family member 5) gene; the parents are heterozygous. Newly designed ARMS PCR followed by direct sequencing confirms the presence of heterozygous in one subject and absence of homozygous novel mutation among randomly selected healthy Saudis. The second family with heterozygous was confirmed with three unexplained RPLs. Pathogenicity analysis of R227I amino acid substitution in ASIC5 protein through molecular docking and interaction analysis revealed that the mutations are highly pathogenic, decrease the stability of the protein, and prevent binding of amiloride, which is an activator to open the acid-sensing ion channel of ASIC5. The identified rare and novel autosomal recessive mutation, c.680G>T:p.R227I (ASIC5Saudi), in two families confirm the ASIC5 gene association with RPL and can be fatal to the fetus.

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Section: Discussionmentioning

confidence: 96%

Whole-Genome Sequencing Reveals Exonic Variation of ASIC5 Gene Results in Recurrent Pregnancy Loss

et al. 2021

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“…Он также активируется наиболее частой мутацией при меланоме, BRAFV600E, тем самым вызывая нарушение регуляции pH во время инициации меланомы. Заболеваемость меланомой растет и в настоящее время является причиной большинства смертей, связанных с раком кожи [9,10].…”

Section: сокращенияunclassified

Principal Components of Genetic Sequences: Correlations and Significance

Ефимов¹,

Efimov²,

Kovaleva³

et al. 2021

Math.Biol.Bioinf.

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Any numerical series can be decomposed into principal components using singular spectral analysis. We have recently proposed a new analysis method ‒ PCA-Seq, which allows calculating numerical principal components for a sequence of elements of any type. In particular, the sequence may be composed of nucleotide base pairs or amino acid residues. Two questions inevitably arise about interpretation of the obtained principal components and about the assessment of their reliability. For interpretation of the symbolic sequence principal components, it is reasonable to evaluate their correlations with numerical characteristics of the sequence elements. To assess the significance of correlations between sequences, one should bear in mind that standard significance criteria are based on the assumption of independence of observations, which, as a rule, is not fulfilled for real sequences. The article discusses the use of an anchor bootstrap technique for these purposes also previously developed by the authors of the article. In this approach it is assumed, that points of a metric space can represent the objects. When taken together they make up some fixed structure in it, in particular, a sequence. The objects are assigned the same random integer weights as in the classical bootstrap. This is sufficient to obtain the bootstrap distribution of the correlation coefficients and assess their significance. The coding sequence of the SLC9A1 gene (synonyms APNH, NHE1, PPP1R143) were taken as an example of use the anchor bootstrap technique in the genetic sequence analysis. Significant correlations of the first principal component were revealed with the hydrophobicity/“transmembraneity” of the corresponding fragments of the amino acid sequence, the phenylalanine content in them, as well as the difference in the T- and A-content in the corresponding nucleotide fragments. Earlier a similar pattern was found by other authors for other genes. Very likely, that it is of a more general nature.

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“…Nevertheless, due to the high number of ion channels and the high complexity of the field, progress in understanding is often slow and focused on single molecules. Specifically in melanoma, the role of ion channels has still not been elucidated in detail [22].…”

Section: Introductionmentioning

confidence: 99%

“…KCa3.1, encoded by the KCNN4 gene, is another member of the Ca 2+ -activated K + channel family, with a smaller single-channel conductance than BK, and lacking any significant voltage dependence. Its aberrant expression has been reported in several cancer types, such as colorectal and pancreatic cancers, where KCa3.1 channels are expressed on the inner mitochondrial membrane, and have been proposed to modulate important mitochondrial functions, such as oxidative phosphorylation [22,[34][35][36][37].…”

Section: Introductionmentioning

confidence: 99%

TRPM2 Oxidation Activates Two Distinct Potassium Channels in Melanoma Cells through Intracellular Calcium Increase

Ferrera

Barbieri

Picco

et al. 2021

IJMS

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Tumor microenvironments are often characterized by an increase in oxidative stress levels. We studied the response to oxidative stimulation in human primary (IGR39) or metastatic (IGR37) cell lines obtained from the same patient, performing patch-clamp recordings, intracellular calcium ([Ca2+]i) imaging, and RT-qPCR gene expression analysis. In IGR39 cells, chloramine-T (Chl-T) activated large K+ currents (KROS) that were partially sensitive to tetraethylammonium (TEA). A large fraction of KROS was inhibited by paxilline—a specific inhibitor of large-conductance Ca2+-activated BK channels. The TEA-insensitive component was inhibited by senicapoc—a specific inhibitor of the Ca2+-activated KCa3.1 channel. Both BK and KCa3.1 activation were mediated by an increase in [Ca2+]i induced by Chl-T. Both KROS and [Ca2+]i increase were inhibited by ACA and clotrimazole—two different inhibitors of the calcium-permeable TRPM2 channel. Surprisingly, IGR37 cells did not exhibit current increase upon the application of Chl-T. Expression analysis confirmed that the genes encoding BK, KCa3.1, and TRPM2 are much more expressed in IGR39 than in IGR37. The potassium currents and [Ca2+]i increase observed in response to the oxidizing agent strongly suggest that these three molecular entities play a major role in the progression of melanoma. Pharmacological targeting of either of these ion channels could be a new strategy to reduce the metastatic potential of melanoma cells, and could complement classical radio- or chemotherapeutic treatments.

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Membrane Transporters and Channels in Melanoma

Cited by 12 publications

References 324 publications

Whole-Genome Sequencing Reveals Exonic Variation of ASIC5 Gene Results in Recurrent Pregnancy Loss

Whole-Genome Sequencing Reveals Exonic Variation of ASIC5 Gene Results in Recurrent Pregnancy Loss

Principal Components of Genetic Sequences: Correlations and Significance

TRPM2 Oxidation Activates Two Distinct Potassium Channels in Melanoma Cells through Intracellular Calcium Increase

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