Voltage-Gated Ptassium Channels Kv1.3 -  Potentially New Molecular Target in Cancer Diagnostics and Therapy

Teisseyre, Andrzej; Gąsiorowska, Justyna; Michalak, Krystyna

doi:10.17219/acem/22339

Cited by 44 publications

(45 citation statements)

References 32 publications

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“…These channels are known mainly for their role in repolarizing (voltage-dependent Kv) the cell membrane following action potentials, which regulate cellular processes such as Ca 2+ signaling, cell volume, secretion, proliferation and migration [69]. Kv channels usually have a homo-tetrameric structure.…”

Section: Toxins and Their Target Of Actionmentioning

confidence: 99%

The Molecular Basis of Toxins’ Interactions with Intracellular Signaling via Discrete Portals

Lahiani

Yavin

Lazarovici

2017

Toxins

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An understanding of the molecular mechanisms by which microbial, plant or animal-secreted toxins exert their action provides the most important element for assessment of human health risks and opens new insights into therapies addressing a plethora of pathologies, ranging from neurological disorders to cancer, using toxinomimetic agents. Recently, molecular and cellular biology dissecting tools have provided a wealth of information on the action of these diverse toxins, yet, an integrated framework to explain their selective toxicity is still lacking. In this review, specific examples of different toxins are emphasized to illustrate the fundamental mechanisms of toxicity at different biochemical, molecular and cellular- levels with particular consideration for the nervous system. The target of primary action has been highlighted and operationally classified into 13 sub-categories. Selected examples of toxins were assigned to each target category, denominated as portal, and the modulation of the different portal’s signaling was featured. The first portal encompasses the plasma membrane lipid domains, which give rise to pores when challenged for example with pardaxin, a fish toxin, or is subject to degradation when enzymes of lipid metabolism such as phospholipases A2 (PLA2) or phospholipase C (PLC) act upon it. Several major portals consist of ion channels, pumps, transporters and ligand gated ionotropic receptors which many toxins act on, disturbing the intracellular ion homeostasis. Another group of portals consists of G-protein-coupled and tyrosine kinase receptors that, upon interaction with discrete toxins, alter second messengers towards pathological levels. Lastly, subcellular organelles such as mitochondria, nucleus, protein- and RNA-synthesis machineries, cytoskeletal networks and exocytic vesicles are also portals targeted and deregulated by other diverse group of toxins. A fundamental concept can be drawn from these seemingly different toxins with respect to the site of action and the secondary messengers and signaling cascades they trigger in the host. While the interaction with the initial portal is largely determined by the chemical nature of the toxin, once inside the cell, several ubiquitous second messengers and protein kinases/ phosphatases pathways are impaired, to attain toxicity. Therefore, toxins represent one of the most promising natural molecules for developing novel therapeutics that selectively target the major cellular portals involved in human physiology and diseases.

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Section: Toxins and Their Target Of Actionmentioning

confidence: 99%

The Molecular Basis of Toxins’ Interactions with Intracellular Signaling via Discrete Portals

Lahiani

Yavin

Lazarovici

2017

Toxins

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Section: Introductionmentioning

confidence: 99%

“…Voltage-gated potassium channels of the Kv1.3 type are integral membrane proteins, which are activated ("open") upon a change in the cell membrane potential, thus enabling a passive fl ux of potassium ions across the cell membrane (5,6). Kv1.3 describes a mammalian shaker-related voltage-gated potassium channel encoded by the KCNA3 gene (6). Studies performed in the last decade provide evidence that Kv1.3 channels are expressed not only in the plasma membrane, but also in the inner mitochondrial membrane (6)(7)(8).…”

Section: Introductionmentioning

confidence: 99%

“…Kv1.3 describes a mammalian shaker-related voltage-gated potassium channel encoded by the KCNA3 gene (6). Studies performed in the last decade provide evidence that Kv1.3 channels are expressed not only in the plasma membrane, but also in the inner mitochondrial membrane (6)(7)(8). The suppression of Kv1.3 channel expression by application of Kv1.3 targeting siRNA signifi cantly reduces the ability of both normal and leukemic T lymphocytes to undergo apoptosis induced by staurosporine (6,9).…”

Section: Introductionmentioning

confidence: 99%

“…Studies performed in the last decade provide evidence that Kv1.3 channels are expressed not only in the plasma membrane, but also in the inner mitochondrial membrane (6)(7)(8). The suppression of Kv1.3 channel expression by application of Kv1.3 targeting siRNA signifi cantly reduces the ability of both normal and leukemic T lymphocytes to undergo apoptosis induced by staurosporine (6,9). The upregulation of channel activity that occurs via the caspase 8-dependent pathway generates a sustained outward current that was required to promote the effl ux of potassium ions and cell shrinkage, which are hallmarks of cell apoptosis (6,10).…”

Section: Introductionmentioning

confidence: 99%

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Inhibition of voltage‑gated potassium channels affect expressions of miR-126 and miR-126* in breast cancer cell lines

Cosan¹,

Soyocak²,

Öner³

2021

BLL

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We aimed to determine the possible correlation between voltage-gated potassium channels and micro RNAs in breast cancer and metastatic breast cancer cells. METHOD: Kv1.3 and Kv10.1 channels were inhibited by specifi c siRNAs using a lipofectamine-based transfection in MCF-7 and MDA-MB-231 cells. After transfection, total RNA was isolated, and then miR-126 and miR-126* expressions were observed using RT-PCR. RESULTS: There was a negative correlation between Kv channels and miRNAs according to the characteristics of the breast cancer cells. The inhibition was observed not only in Kv1.3 but also in Kv10.1 in MCF-7 cells, and miR-126 and miR-126* expressions were downregulated compared to the control group (p < 0.001). The inhibition of these channels in MDA-MB-231 cells caused an upregulation of miR-126 and miR-126* expressions (p < 0.001). CONCLUSION: The miR-126 and miR-126* expressions differed according to benign and malign breast cancer cell lines. Furthermore, we found that miR-126/126* may interact with Kv1.3 and Kv10.1 voltage-gated potassium channels. Our study suggests and indicates the relationship between Kv channels and miRNAs in breast cancer cells (Tab. 1, Fig. 2, Ref. 51).

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Toward Hijacking Bioelectricity in Cancer to Develop New Bioelectronic Medicine

Robinson

Jain

Sherman

et al. 2021

Advanced Therapeutics

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Bioelectronic medicine is a treatment modality that uses electricity to treat disease by altering the body's electrical communication systems. All cells are electrically active, in that they possess bioelectric circuitry generating a resting membrane potential and endogenous electric fields that influence cell functions and communication. There is now an accepted paradigm that cancer is characterized by malfunctions in cells' bioelectrical circuitry. This yields opportunities for bioelectronic medicine as novel treatments for cancer by manipulating its bioelectrical properties. To highlight the possibilities a bioelectrical approach can offer cancer therapy, the relevance of bioelectrical activity in cancer is reviewed and also how such activity can be hijacked in novel treatments. This includes sensing or measuring the electrical activity of cells for diagnostic and prognostic applications, controlling or altering bioelectricity including both ionic and faradaic current processes, and eliciting morphological changes using electric fields. Importantly, key links between cellular ionic and faradaic processes that contribute to cancer phenotypes are presented, which if considered and understood as a whole, can bring broad-reaching improvements to cancer therapy.

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Voltage-Gated Ptassium Channels Kv1.3 - Potentially New Molecular Target in Cancer Diagnostics and Therapy

Cited by 44 publications

References 32 publications

The Molecular Basis of Toxins’ Interactions with Intracellular Signaling via Discrete Portals

The Molecular Basis of Toxins’ Interactions with Intracellular Signaling via Discrete Portals

Inhibition of voltage‑gated potassium channels affect expressions of miR-126 and miR-126* in breast cancer cell lines

Toward Hijacking Bioelectricity in Cancer to Develop New Bioelectronic Medicine

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