Ion Channels in Gliomas—From Molecular Basis to Treatment

Elias, Abdallah F.; Lin, Bernice C.; Piggott, Beverly J.

doi:10.3390/ijms24032530

Cited by 10 publications

(7 citation statements)

References 358 publications

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“…As TRAM-34 had a negligible effect on the cell cycle of unirradiated T98G cells, the above results are in agreement with Abdullaev et al (2010). The presence and functional significance of KCa3.1 on gliomas, regarding proliferation as well as migration and invasion is also reviewed by Elias et al [128].…”

Section: Kca31 Inhibitors Affect Proliferative Capacity On Irradiated...supporting

confidence: 74%

Kca3.1-Related Cellular Signalling Involved in Cancer Proliferation

Calderón,

Arvelo

2024

Cell Physiol Biochem

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Anomalous expression of potassium channels in cancer tissues is associated with several cancer hallmarks that support deregulated proliferation and tumor progression. Ion channels seem to influence cell proliferation; however, the crucial molecular mechanisms involved remain elusive. Some results show how extracellular mitogenic signals modulate ion channel activity through intracellular secondary messengers. It is relevant because we are beginning to understand how potassium channels can affect the proliferative capacity of cells, either in normal mitogen-dependent proliferation or in mitogen-unresponsive proliferation. Calcium- dependent potassium channels have been implicated in cell cycle signaling in many cancerous cell lines. In particular, the so-called intermediate conductance KCa3.1 (IKCa) is reported to play a significant role in uncontrolled cell cycle signaling, among other malignant processes driven by cancer hallmarks. In addition to these features, this channel can be subjected to specific pharmacological regulation, making it a promising cornerstone for understanding the signaling behavior of several types of cancer and as a target for chemotherapeutic approaches. This review is dedicated to the connection of KCa3.1 activity, in canonical and non-canonical ways, to the cell cycle signaling, including the cooperation with calcium channels to generate calcium signals and its role as a mediator of proliferative signals.

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Section: Kca31 Inhibitors Affect Proliferative Capacity On Irradiated...supporting

confidence: 74%

Kca3.1-Related Cellular Signalling Involved in Cancer Proliferation

Calderón,

Arvelo

2024

Cell Physiol Biochem

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“…The role of the BK Ca channel in glioblastoma, including U-87 MG cells, is being investigated in various aspects, such as its role in cell proliferation or migration. These analyses are part of a wide range of research on the role of potassium channels in cancer cells [ 42 , 43 ]. The use of the CRISPR/Cas9 technique results in the removal of the BK Ca channel from all cellular compartments, including the plasma membrane and mitochondria.…”

Section: Discussionmentioning

confidence: 99%

Loss of the large conductance calcium-activated potassium channel causes an increase in mitochondrial reactive oxygen species in glioblastoma cells

Kulawiak

Żochowska

Bednarczyk

et al. 2023

Pflugers Arch - Eur J Physiol

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Mitochondrial potassium (mitoK) channels play an important role in cellular physiology. These channels are expressed in healthy tissues and cancer cells. Activation of mitoK channels can protect neurons and cardiac tissue against injury induced by ischemia–reperfusion. In cancer cells, inhibition of mitoK channels leads to an increase in mitochondrial reactive oxygen species, which leads to cell death. In glioma cell activity of the mitochondrial, large conductance calcium-activated potassium (mitoBKCa) channel is regulated by the mitochondrial respiratory chain. In our project, we used CRISPR/Cas9 technology in human glioblastoma U-87 MG cells to generate knockout cell lines lacking the α-subunit of the BKCa channel encoded by the KCNMA1 gene, which also encodes cardiac mitoBKCa. Mitochondrial patch-clamp experiments showed the absence of an active mitoBKCa channel in knockout cells. Additionally, the absence of this channel resulted in increased levels of mitochondrial reactive oxygen species. However, analysis of the mitochondrial respiration rate did not show significant changes in oxygen consumption in the cell lines lacking BKCa channels compared to the wild-type U-87 MG cell line. These observations were reflected in the expression levels of selected mitochondrial genes, organization of the respiratory chain, and mitochondrial morphology, which did not show significant differences between the analyzed cell lines. In conclusion, we show that in U-87 MG cells, the pore-forming subunit of the mitoBKCa channel is encoded by the KCNMA1 gene. Additionally, the presence of this channel is important for the regulation of reactive oxygen species levels in mitochondria.

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“…Various studies have demonstrated that AQPs 1, 4, and 9, as well as voltage-gated potassium, sodium, calcium, chloride, and acid-sensing ion channels are overactivated in GBM and can contribute to control of cell volume, degradation of extracellular matrix, rearrangement of the cytoskeleton, protrusion of lamellipodia and filopodia, and shifting of focal assembly sites and cell-cell adhesions [ 165 , 166 ]. Volume changes, primarily regulated by ion channels activity, are thought to be crucial in modulating tumor cell invasion in tight areas and the dynamics of cellular migration [ 167 ].…”

Section: Therapeutic Targets Of Glioma Invasionmentioning

confidence: 99%

Intrinsic and Microenvironmental Drivers of Glioblastoma Invasion

De Fazio,

Pittarello,

Gans

et al. 2024

IJMS

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Gliomas are diffusely infiltrating brain tumors whose prognosis is strongly influenced by their extent of invasion into the surrounding brain tissue. While lower-grade gliomas present more circumscribed borders, high-grade gliomas are aggressive tumors with widespread brain infiltration and dissemination. Glioblastoma (GBM) is known for its high invasiveness and association with poor prognosis. Its low survival rate is due to the certainty of its recurrence, caused by microscopic brain infiltration which makes surgical eradication unattainable. New insights into GBM biology at the single-cell level have enabled the identification of mechanisms exploited by glioma cells for brain invasion. In this review, we explore the current understanding of several molecular pathways and mechanisms used by tumor cells to invade normal brain tissue. We address the intrinsic biological drivers of tumor cell invasion, by tackling how tumor cells interact with each other and with the tumor microenvironment (TME). We focus on the recently discovered neuronal niche in the TME, including local as well as distant neurons, contributing to glioma growth and invasion. We then address the mechanisms of invasion promoted by astrocytes and immune cells. Finally, we review the current literature on the therapeutic targeting of the molecular mechanisms of invasion.

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Ion Channels in Gliomas—From Molecular Basis to Treatment

Cited by 10 publications

References 358 publications

Kca3.1-Related Cellular Signalling Involved in Cancer Proliferation

Kca3.1-Related Cellular Signalling Involved in Cancer Proliferation

Loss of the large conductance calcium-activated potassium channel causes an increase in mitochondrial reactive oxygen species in glioblastoma cells

Intrinsic and Microenvironmental Drivers of Glioblastoma Invasion

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