Role of ion channels during cell division

Rosendo-Pineda, Margarita Jacaranda; Moreno, Cláudia; Vaca, Luis

doi:10.1016/j.ceca.2020.102258

Cited by 37 publications

(29 citation statements)

References 90 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Therefore, genetic alterations affecting VRAC components may not only lead to decreased cisplatin uptake but also changes in apoptosis induction also in other tumor entities [ 13 ]. The dual role of cell volume regulation and active transport of platinum-based drugs may be important for the cancer cells to adapt to the tumor microenvironment and fine tune cell cycle, migration, and metastasis, particularly in the absence of the cisplatin drug selection pressure [ 13 , 36 , 37 , 38 ].…”

Section: Discussionmentioning

confidence: 99%

Profiling Cisplatin Resistance in Head and Neck Cancer: A Critical Role of the VRAC Ion Channel for Chemoresistance

Siemer

Fauth

Scholz

et al. 2021

Cancers

View full text Add to dashboard Cite

Treatment success of head and neck cancers (HNSCC) is often hindered by tumor relapses due to therapy resistances. This study aimed at profiling cisplatin resistance mechanisms and identifying biomarkers potentially suitable as drug targets and for patient stratification. Bioinformatic analyses of suggested resistance factors in a cohort of 565 HNSCC patients identified the VRAC ion channel as a clinically relevant indicator for recurrent diseases following radiochemotherapy (p = 0.042). Other drug import/export transporters, such as CTR1, OCT1, or MRP1, were found to be less relevant. To experimentally verify VRAC’s critical role for cisplatin resistance, we used CRISPR/Cas9 knockout resulting in cisplatin-resistant HNSCC cells, which could be resensitized by VRAC expression. Next-generation sequencing further underlined VRAC’s importance and identified VRAC-regulated signaling networks, potentially also contributing to cisplatin resistance. CTR1, OCT1, or MRP1 did not contribute to increased cisplatin resistance. In addition to two-dimensional HNSCC models, three-dimensional tumor spheroid cultures confirmed VRAC’s unique role for cisplatin sensitivity. Here, resistance correlated with DNA damage and downstream apoptosis. The cisplatin specificity of the identified VRAC pathway was verified by testing paclitaxel and doxorubicin. Our results were independently confirmed in naturally occurring, cisplatin-resistant HNSCC cancer cell models. Collectively, we here demonstrate VRAC’s role for cisplatin resistance in HNSCC and its relevance as a potential drug target and/or prognostic biomarker for chemotherapy resistance.

show abstract

Section: Discussionmentioning

confidence: 99%

Profiling Cisplatin Resistance in Head and Neck Cancer: A Critical Role of the VRAC Ion Channel for Chemoresistance

Siemer

Fauth

Scholz

et al. 2021

Cancers

View full text Add to dashboard Cite

show abstract

“…Ion channels play a key role in cell division and differentiation [50]. These channels need to be tightly regulated to maintain the fate and physiological role of cells.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of BK_Ca channels protects neonatal hearts against myocardial ischemia and reperfusion injury

Sanghvi

Szteyn

Ponnalagu

et al. 2021

Preprint

View full text Add to dashboard Cite

BKCa channels are large-conductance calcium and voltage-activated potassium channels that are heterogeneously expressed in a wide array of cells. Activation of BKCa channels present in mitochondria of adult ventricular cardiomyocytes is implicated in cardioprotection against ischemia-reperfusion (IR) injury. However, the BKCa channel’s activity has never been detected in the plasma membrane of adult ventricular cardiomyocytes. In this study, we report the presence of the BKCa channel in the plasma membrane and mitochondria of neonatal murine and rodent cardiomyocytes which protects the heart on inhibition but not activation. Furthermore, K+ currents measured in neonatal cardiomyocyte (NCM) was sensitive to iberiotoxin (IbTx), suggesting the presence of BKCa channels in the plasma membrane. Neonatal hearts subjected to IR when post-conditioned with NS1619 during reoxygenation increased the myocardial infarction whereas IbTx reduced the infarct size. In agreement, isolated NCM also presented increased apoptosis on treatment with NS1619 during hypoxia and reoxygenation, whereas IbTx reduced TUNEL positive cells. In NCMs, activation of BKCa channels increased the intracellular reactive oxygen species post HR injury. Electrophysiological characterization of NCMs indicated that NS1619 increased the beat period, field, and action potential duration, and decreased the conduction velocity and spike amplitude. In contrast, IbTx had no impact on the electrophysiological properties of NCMs. Taken together, our data established that inhibition of plasma membrane BKCa channels in the NCM protects neonatal heart/cardiomyocytes from IR injury. Furthermore, the functional disparity observed towards the cardioprotective activity of BKCa channels in adults compared to neonatal heart could be attributed to their differential localization.

show abstract

“…A cell that needs to divide enters the cell cycle, and the regulation of the progression from one phase to the next one has been proposed to be coupled to environmental conditions so that this occurs only when it is necessary [60]. It is also known that the activity and expression of ion channels change during the cell cycle, and that Ca2+ concentration increases at the 3 cell cycle checkpoints and the membrane depolarizes between G2 and Mitosis, as reviewed by Rosendo-Pineda et al [61]. We decided therefore to analyze whether the L/R tumors presented proliferation differences.…”

Section: Proliferation Differencesmentioning

confidence: 99%

When Left Does Not Seem Right: Epigenetic and Bioelectric Differences Between Left- and Right-Sided Breast Cancer

Masuelli

Real

Campoy

et al. 2021

Preprint

View full text Add to dashboard Cite

Background: During embryogenesis, lateral symmetry is broken giving rise to Left/Right (L/R) breast tissues with distinct identity. L/R-sided breast tumors exhibit consistently-biased incidence, gene expression, and DNA methylation. We postulate that a differential L/R tumor-microenvironment crosstalk generates different tumorigenesis mechanisms. Methods: We performed in-silico analyses on breast tumors of public datasets, developed xenografted tumors, and conditioned MDA-MB-231 cells with L/R mammary extracts. Results: We found L/R differential DNA methylation involved in embryogenic and neuron-like functions. Focusing on ion-channels, we discovered significant L/R epigenetic and bioelectric differences. Specifically, L-sided cells presented increased methylation of hyperpolarizing ion channel genes and increased Ca2+ concentration and depolarized membrane potential, compared to R-ones. Functional consequences were associated with increased proliferation in left tumors, assessed by KI67 expression and mitotic count. Conclusions: Our findings reveal considerable L/R asymmetry in cancer processes, and suggest specific L/R epigenetic and bioelectric differences as future targets for cancer therapeutic approaches in the breast and many other paired organs.

show abstract

Role of ion channels during cell division

Cited by 37 publications

References 90 publications

Profiling Cisplatin Resistance in Head and Neck Cancer: A Critical Role of the VRAC Ion Channel for Chemoresistance

Profiling Cisplatin Resistance in Head and Neck Cancer: A Critical Role of the VRAC Ion Channel for Chemoresistance

Inhibition of BK_Ca channels protects neonatal hearts against myocardial ischemia and reperfusion injury

When Left Does Not Seem Right: Epigenetic and Bioelectric Differences Between Left- and Right-Sided Breast Cancer

Contact Info

Product

Resources

About

Role of ion channels during cell division

Cited by 37 publications

References 90 publications

Profiling Cisplatin Resistance in Head and Neck Cancer: A Critical Role of the VRAC Ion Channel for Chemoresistance

Profiling Cisplatin Resistance in Head and Neck Cancer: A Critical Role of the VRAC Ion Channel for Chemoresistance

Inhibition of BKCa channels protects neonatal hearts against myocardial ischemia and reperfusion injury

When Left Does Not Seem Right: Epigenetic and Bioelectric Differences Between Left- and Right-Sided Breast Cancer

Contact Info

Product

Resources

About

Inhibition of BK_Ca channels protects neonatal hearts against myocardial ischemia and reperfusion injury