Functional expression of mitochondrial KCa3.1 channels in non-small cell lung cancer cells

Bulk, Etmar; Todesca, Luca Matteo; Bachmann, Magdalena; Szabó, Ildikò; Rieke, Marius; Schwab, Albrecht

doi:10.1007/s00424-022-02748-x

Cited by 8 publications

(12 citation statements)

References 52 publications

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“…4). As shown previously ROS release rises in senicapoc-treated A549 cells after ~ 40 min ( uorescence increase compared to baseline values: control 22.9 ± 4.3% vs senicapoc 88.2 ± 25.4%) as shown previously (Bulk 2022). Following double treatment with erlotinib and senicapoc this occurs after 30 min (18.6 ± 4.9% control vs 102.3 ± 41.3% senicapoc and erlotinib; Fig.…”

Section: Senicapoc In Combination With Erlotinib Induces Ros Release ...supporting

confidence: 86%

Targeting KCa3.1 channels to overcome erlotinib resistance in non-small cell lung cancer cells

Todesca,

Gerke,

Bulk

et al. 2023

Preprint

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Almost all non-small cell lung cancer (NSCLC) patients initially responding to EGFR tyrosine kinase inhibitors (TKIs) develop acquired resistance. Since KCa3.1 channels, expressed in mitochondria and plasma membrane, regulate similar behavioral traits of NSCLC cells as EGFR, we hypothesized that their blockade contributes to overcoming EGFR-TKI resistance. Meta-analysis of microarray data revealed that KCa3.1 channel expression in erlotinib-resistant NSCLC cells correlates with that of genes of integrin and apoptosis pathways. Using erlotinib-sensitive and –resistant NSCLC cells we monitored the role of mitochondrial KCa3.1 channels in integrin signaling by studying cell-matrix adhesion with single-cell force spectroscopy. Apoptosis was quantified with fluorescence-based assays. The function of mitochondrial KCa3.1 channels in these processes was assessed by measuring the mitochondrial membrane potential and by quantifying ROS production. Functional assays were supplemented by biochemical analyses. We show that KCa3.1 channel inhibition with senicapoc in erlotinib-resistant NSCLC cells increases cell adhesion by increasing β1-integrin expression, that in turn depends on mitochondrial ROS release. Increased adhesion impairs migration of NSCLC cells in a 3D matrix. At the same time, the senicapoc-dependent ROS production induces cytochrome C release and triggers apoptosis of erlotinib-resistant NSCLC cells. Thus, KCa3.1 channel blockade overcomes EGFR-TKI resistance by inhibiting NSCLC motility and inducing apoptosis.

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Section: Senicapoc In Combination With Erlotinib Induces Ros Release ...supporting

confidence: 86%

Targeting KCa3.1 channels to overcome erlotinib resistance in non-small cell lung cancer cells

Todesca,

Gerke,

Bulk

et al. 2023

Preprint

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“…This overexpression is related to promalignant properties of the channel. Moreover, the studies [135,136] confirmed the localisation of the K Ca channels in the inner mitochondrial membrane in human colon and lung cancer cells. Likewise the Kv1.3 channels, inhibition of K Ca s (along with other anti-cancer drug administration) caused enhancement of apoptosis.…”

Section: Mitochondrial Potassium Channelsmentioning

confidence: 63%

Potassium Channels, Glucose Metabolism and Glycosylation in Cancer Cells

Wawrzkiewicz-Jałowiecka

Lalik

Łukasiak

et al. 2023

IJMS

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Potassium channels emerge as one of the crucial groups of proteins that shape the biology of cancer cells. Their involvement in processes like cell growth, migration, or electric signaling, seems obvious. However, the relationship between the function of K+ channels, glucose metabolism, and cancer glycome appears much more intriguing. Among the typical hallmarks of cancer, one can mention the switch to aerobic glycolysis as the most favorable mechanism for glucose metabolism and glycome alterations. This review outlines the interconnections between the expression and activity of potassium channels, carbohydrate metabolism, and altered glycosylation in cancer cells, which have not been broadly discussed in the literature hitherto. Moreover, we propose the potential mediators for the described relations (e.g., enzymes, microRNAs) and the novel promising directions (e.g., glycans-orinented drugs) for further research.

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“…The only member of the Calcium activated subfamily that has been shown to be expressed in NSCLC is KCa3.1 ( Bulk et al, 2015 ; 2017 ; 2022 ; Xu et al, 2021 ) ( Table 4 ). In particular, increased expression of the channel was detected in more aggressive cells ( Bulk et al, 2015 ) where it also regulates ICAM-1 dependent cell-cell adhesion between endothelial and cancer cells ( Bulk et al, 2017 ).…”

Section: Ion Channels In Human Cancermentioning

confidence: 99%

Ion channels in lung cancer: biological and clinical relevance

Capitani,

Chioccioli Altadonna,

Santillo

et al. 2023

Front. Pharmacol.

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Despite improvements in treatment, lung cancer is still a major health problem worldwide. Among lung cancer subtypes, the most frequent is represented by adenocarcinoma (belonging to the Non-Small Cell Lung Cancer class) although the most challenging and harder to treat is represented by Small Cell Lung Cancer, that occurs at lower frequency but has the worst prognosis. For these reasons, the standard of care for these patients is represented by a combination of surgery, radiation therapy and chemotherapy. In this view, searching for novel biomarkers that might help both in diagnosis and therapy is mandatory. In the last 30 years it was demonstrated that different families of ion channels are overexpressed in both lung cancer cell lines and primary tumours. The altered ion channel profile may be advantageous for diagnostic and therapeutic purposes since most of them are localised on the plasma membrane thus their detection is quite easy, as well as their block with specific drugs and antibodies. This review focuses on ion channels (Potassium, Sodium, Calcium, Chloride, Anion and Nicotinic Acetylcholine receptors) in lung cancer (both Non-Small Cell Lung Cancer and Small Cell Lung Cancer) and recapitulate the up-to-date knowledge about their role and clinical relevance for a potential use in the clinical setting, for lung cancer diagnosis and therapy.

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Functional expression of mitochondrial KCa3.1 channels in non-small cell lung cancer cells

Cited by 8 publications

References 52 publications

Targeting KCa3.1 channels to overcome erlotinib resistance in non-small cell lung cancer cells

Targeting KCa3.1 channels to overcome erlotinib resistance in non-small cell lung cancer cells

Potassium Channels, Glucose Metabolism and Glycosylation in Cancer Cells

Ion channels in lung cancer: biological and clinical relevance

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