Transcriptional regulation of KCNA2 coding Kv1.2 by EWS::FLI1: involvement in controlling the YAP/Hippo signalling pathway and cell proliferation.

Background: Ewing sarcoma (ES), the second main pediatric bone sarcoma, is characterised by a chromosomal translocation leading to the formation of fusion proteins like EWS::FLI1. While several studies have shown that potassium channels drive the development of many tumours, limited data exist on ES. This work therefore aimed to study the transcriptional regulation of KCNA2 and define the involvement of the Kv1.

Chimeric protein EWS::FLI1 drives cell proliferation in Ewing Sarcoma via aberrant expression of KCNN1/SK1 and dysregulation of calcium signaling.

Ewing sarcoma (ES) is characterized by EWS::FLI1 or EWS::ERG fusion proteins. Knowing that ion channels are involved in tumorigenesis, this work aimed to study the involvement of the KCNN1 gene, which encodes the SK1 potassium channel, in ES development. Bioinformatics analyses from databases were used to study KCNN1 expression in patients and cell lines.

Plasma membrane SK2 channel activity regulates migration and chemosensitivity of high-grade serous ovarian cancer cells.

No data are currently available on the functional role of small conductance Ca-activated K channels (SKCa) in ovarian cancer. Here, we characterized the role of SK2 (KCa2.2) in ovarian cancer cell migration and chemosensitivity.

Enhanced macromolecular substance extravasation through the blood-brain barrier via acoustic bubble-cell interactions.

The blood-brain barrier (BBB) maintains brain homeostasis, regulates influx and efflux transport, and provides protection to the brain tissue. Ultrasound (US) and microbubble (MB)-mediated blood-brain barrier opening is an effective and safe technique for drug delivery in-vitro and in-vivo. However, the exact mechanism underlying this technique is still not fully elucidated.

A multiple-oscillator mechanism underlies antigen-induced Ca oscillations in Jurkat T-cells.

T-cell receptor stimulation triggers cytosolic Ca signaling by inositol-1,4,5-trisphosphate (IP)-mediated Ca release from the endoplasmic reticulum (ER) and Ca entry through Ca release-activated Ca (CRAC) channels gated by ER-located stromal-interacting molecules (STIM1/2). Physiologically, cytosolic Ca signaling manifests as regenerative Ca oscillations, which are critical for nuclear factor of activated T-cells-mediated transcription. In most cells, Ca oscillations are thought to originate from IP receptor-mediated Ca release, with CRAC channels indirectly sustaining them through ER refilling.

SK- and Kv1-type potassium channels and cancer: Promising therapeutic targets?

Ion channels are transmembrane structures that allow the passage of ions across cell membranes such as the plasma membrane or the membranes of various organelles like the nucleus, endoplasmic reticulum, Golgi apparatus or mitochondria. Aberrant expression of various ion channels has been demonstrated in several tumor cells, leading to the promotion of key functions in tumor development, such as cell proliferation, resistance to apoptosis, angiogenesis, invasion and metastasis. The link between ion channels and these key biological functions that promote tumor development has led to the classification of cancers as oncochannelopathies.

Pivotal role of the ORAI3-STIM2 complex in the control of mitotic death and prostate cancer cell cycle progression.

Prostate cancer (PCa) represents one of the most frequent diagnosed cancer in males worldwide. Due to routine screening tests and the efficiency of available treatments, PCa-related deaths have significantly decreased over the past decades. However, PCa remains a critical threat if detected at a late stage in which, cancer cells would have already detached from the primary tumor to spread and invade other parts of the body.

Direct Cell Death Induced by CD20 Monoclonal Antibodies on B Cell Lymphoma Cells Revealed by New Protocols of Analysis.

CD20 monoclonal antibodies (mAbs) eliminate B cells in several clinical contexts. At least two of these Abs, obinutuzumab (OBI) and rituximab (RTX), induce quick elimination of targets and put cancer patients at risk of tumor lysis syndrome (TLS) within 12-24 h of the first dose. The mechanisms of killing can require the recruiting of effector mechanisms from the patient's immune system, but they can induce direct killing as well.

Calcium signaling: A therapeutic target to overcome resistance to therapies in cancer.

Innate and acquired resistances to therapeutic agents are responsible for the failure of cancer treatments. Due to the multifactorial nature of resistance, the identification of new therapeutic targets is required to improve cancer treatment. Calcium is a universal second messenger that regulates many cellular functions such as proliferation, migration, and survival.

The Sodium-Calcium Exchanger Controls the Membrane Potential of AFT024: A Mesenchymal Stem Cell Hematopoietic Niche Forming Line.

The aim of this study was to characterize the functional expression of sodium-calcium exchangers on AFT024 cell line, a murine model of mesenchymal stem/stromal cells (MSCs) supporting human primitive hematopoiesis. All current-clamp and voltage-clamp experiments were performed using the perforated patch whole-cell recording technique with amphotericin B. The membrane potential of -14 mV shifted to -35 mV when lowering the external sodium concentration to 0.

Data pertaining to aberrant intracellular calcium handling during androgen deprivation therapy in prostate cancer.

The data generated here in relates to the research article "CaV1.3 enhanced store operated calcium promotes resistance to androgen deprivation in prostate cancer". A model of prostate cancer (PCa) progression to castration resistance was employed, with untreated androgen sensitive LNCaP cell line alongside two androgen deprived (bicalutamide) sublines, either 10 days (LNCaP-ADT) or 2 years (LNCaP-ABL) treatment, in addition to androgen insensitive PC3.

CaV1.3 enhanced store operated calcium promotes resistance to androgen deprivation in prostate cancer.

Androgen deprivation therapy (ADT) is the main treatment for advanced prostate cancer (PCa) but resistance results in progression to terminal castrate resistant PCa (CRPC), where there is an unmet therapeutic need. Aberrant intracellular calcium (Ca) is known to promote neoplastic transformation and treatment resistance. There is growing evidence that voltage gated calcium channel (VGCC) expression is increased in cancer, particularly CACNA1D/CaV1.

Strengthening Anti-Glioblastoma Effect by Multi-Branched Dendrimers Design of a Scorpion Venom Tetrapeptide.

Glioblastoma is the most aggressive and invasive form of central nervous system tumors due to the complexity of the intracellular mechanisms and molecular alterations involved in its progression. Unfortunately, current therapies are unable to stop its neoplastic development. In this context, we previously identified and characterized AaTs-1, a tetrapeptide (IWKS) from scorpion venom, which displayed an anti-proliferative effect against U87 cells with an IC value of 0.

AaTs-1: A Tetrapeptide from Scorpion Venom, Inhibiting U87 Glioblastoma Cells Proliferation by p53 and FPRL-1 Up-Regulations.

Glioblastoma is an aggressive cancer, against which medical professionals are still quite helpless, due to its resistance to current treatments. Scorpion toxins have been proposed as a promising alternative for the development of effective targeted glioblastoma therapy and diagnostic. However, the exploitation of the long peptides could present disadvantages.

Zeb1 and SK3 Channel Are Up-Regulated in Castration-Resistant Prostate Cancer and Promote Neuroendocrine Differentiation.

Therapeutic strategies for metastatic castration-resistant prostate cancer aim to target androgen receptor signaling. Despite initial survival benefits, treatment resistance invariably occurs, leading to lethal disease. Therapies targeting the androgen receptor can induce the emergence of a neuroendocrine phenotype and reactivate embryonic programs associated with epithelial to mesenchymal transition.

Calcium Channel Blockers Impair the Antitumor Activity of Anti-CD20 Monoclonal Antibodies by Blocking EGR-1 Induction.

Direct cell death induction, in addition to immune-effector cell-mediated mechanisms, is one of the key mechanisms of action of anti-CD20 antibodies, and yet the signaling pathways implicated remain poorly investigated. Here we show that the transcription factor EGR-1 is rapidly induced by anti-CD20 antibodies and is a key mediator for CD20-induced cell death. EGR-1 induction results from an increased calcium influx induced by anti-CD20 antibodies.

Potassium and Calcium Channel Complexes as Novel Targets for Cancer Research.

The intracellular Ca concentration is mainly controlled by Ca channels. These channels form complexes with K channels, which function to amplify Ca flux. In cancer cells, voltage-gated/voltage-dependent Ca channels and non-voltage-gated/voltage-independent Ca channels have been reported to interact with K channels such as Ca-activated K channels and voltage-gated K channels.

Hypoxia Promotes Prostate Cancer Aggressiveness by Upregulating EMT-Activator Zeb1 and SK3 Channel Expression.

Hypoxia is a well-established feature of prostate cancer (PCa) and is associated with disease aggressiveness. The hypoxic microenvironment initiates multiple adaptive responses including epithelial-to-mesenchymal transition (EMT) and a remodeling of calcium homeostasis involved in cancer progression. In the present study, we identified a new hypoxia signaling pathway with a positive feedback loop between the EMT transcription factor Zeb1 and SK3, a Ca-activated K+ channel, which leads to amplifying store-operated Ca entry.

Roles of endogenous ether lipids and associated PUFAs in the regulation of ion channels and their relevance for disease.

Ether lipids (ELs) are lipids characterized by the presence of either an ether linkage (alkyl lipids) or a vinyl ether linkage [i.e., plasmalogens (Pls)] at the 1 position of the glycerol backbone, and they are enriched in PUFAs at the 2 position.

Mitochondrial Calcium Regulation of Redox Signaling in Cancer.

Calcium (Ca) uptake into the mitochondria shapes cellular Ca signals and acts as a key effector for ATP generation. In addition, mitochondria-derived reactive oxygen species (mROS), produced as a consequence of ATP synthesis at the electron transport chain (ETC), modulate cellular signaling pathways that contribute to many cellular processes. Cancer cells modulate mitochondrial Ca ([Ca]m) homeostasis by altering the expression and function of mitochondrial Ca channels and transporters required for the uptake and extrusion of mitochondrial Ca.

Lipidic synthetic alkaloids as SK3 channel modulators. Synthesis and biological evaluation of 2-substituted tetrahydropyridine derivatives with potential anti-metastatic activity.

Small Conductance Calcium (Ca)-activated potassium (K) channels (SKCa) are now proved to be involved in many cancer cell behaviors such as proliferation or migration. The SK3 channel isoform was particularly described in breast cancer where it can be associated with the Orai1 Ca channel to form a complex that regulates the Ca homeostasis during tumor development and acts as a potent mediator of bone metastases development in vivo. Until now, very few specific blockers of Orai1 and/or SK3 have been developed as potential anti-metastatic compounds.

A Novel Calcium-Mediated EMT Pathway Controlled by Lipids: An Opportunity for Prostate Cancer Adjuvant Therapy.

The composition of periprostatic adipose tissue (PPAT) has been shown to play a role in prostate cancer (PCa) progression. We recently reported an inverse association between PCa aggressiveness and elevated PPAT linoleic acid (LA) and eicosapentaenoic acid (EPA) content. In the present study, we identified a new signaling pathway with a positive feedback loop between the epithelial-to-mesenchymal transition (EMT) transcription factor Zeb1 and the Ca-activated K channel SK3, which leads to an amplification of Ca entry and cellular migration.

Lipid metabolism and Calcium signaling in epithelial ovarian cancer.

Epithelial Ovarian cancer (EOC) is the deadliest gynecologic malignancy and represents the fifth leading cause of all cancer-related deaths in women. The majority of patients are diagnosed at an advanced stage of the disease that has spread beyond the ovaries to the peritoneum or to distant organs (stage FIGO III-IV) with a 5-year overall survival of about 29%. Consequently, it is necessary to understand the pathogenesis of this disease.