Publications
341 results found
Vysokov NV, Silva J-P, Lelianova VG, et al., 2016, The Mechanism of Regulated Release of Lasso/Teneurin-2, Frontiers in Molecular Neuroscience, Vol: 9, ISSN: 1662-5099
Teneurins are large cell-surface receptors involved in axon guidance. Teneurin-2 (also known as latrophilin-1-associated synaptic surface organizer (Lasso)) interacts across the synaptic cleft with presynaptic latrophilin-1, an adhesion G-protein-coupled receptor that participates in regulating neurotransmitter release. Lasso-latrophilin-1 interaction mediates synapse formation and calcium signaling, highlighting the important role of this trans-synaptic receptor pair. However, Lasso is thought to be proteolytically cleaved within its ectodomain and released into the medium, making it unclear whether it acts as a proper cell-surface receptor or a soluble protein. We demonstrate here that during its intracellular processing Lasso is constitutively cleaved at a furin site within its ectodomain. The cleaved fragment, which encompasses almost the entire ectodomain of Lasso, is potentially soluble; however, it remains anchored on the cell surface via its non-covalent interaction with the transmembrane fragment of Lasso. Lasso is also constitutively cleaved within the intracellular domain (ICD). Finally, Lasso can be further proteolytically cleaved within the transmembrane domain. The third cleavage is regulated and releases the entire ectodomain of Lasso into the medium. The released ectodomain of Lasso retains its functional properties and binds latrophilin-1 expressed on other cells; this binding stimulates intracellular Ca2+ signaling in the target cells. Thus, Lasso not only serves as a bona fide cell-surface receptor, but also as a partially released target-derived signaling factor.
Djamgoz MB, Pardo LA, 2016, Ion channels, transporters and cancer ("INCA2015"): an international meeting in honor of Prof. Dr. Walter Stühmer., European Biophysics Journal, ISSN: 0175-7571
Aydar E, Stratton D, Fraser SP, et al., 2016, Sigma-1 receptors modulate neonatal Nav1.5 ion channels in breast cancer cell lines., European Biophysics Journal, ISSN: 0175-7571
The main aim of this study was to investigate a possible functional connection between sigma-1 receptors and voltage-gated sodium channels (VGSCs) in human breast cancer cells. The hypothesis was that sigma-1 drugs could alter the metastatic properties of breast cancer cells via the VGSC. Evidence was found for expression of sigma-1 receptor and neonatal Nav1.5 (nNav1.5) expression in both MDA-MB-231 and MDA-MB-468 cells. Sigma-1 drugs (SKF10047 and dimethyltryptamine) did not affect cell proliferation or migration but significantly reduced adhesion to the substrate. Silencing sigma-1 receptor expression by siRNA similarly reduced the adhesion. Blocking nNav1.5 activity with a polyclonal antibody (NESOpAb) targeting an extracellular region of nNav1.5 also reduced the adhesion in both cell lines. Importantly, the results of combined treatments with NESOpAb and a sigma-1 drug or sigma-1 siRNA suggested that both treatments targeted the same mechanism. The possibility was tested, therefore, that the sigma-1 receptor and the nNav1.5 channel formed a physical, functional complex. This suggestion was supported by the results of co-immunoprecipitation experiments. Furthermore, application of sigma-1 drugs to the cells reduced the surface expression of nNav1.5 protein, which could explain how sigma-1 receptor activation could alter the metastatic behaviour of breast cancer cells. Overall, these results are consistent with the idea of a sigma-1 protein behaving like either a "chaperone" or a regulatory subunit associated with nNav1.5.
Bugan I, Karagoz Z, Altun S, et al., 2016, Gabapentin, an Analgesic Used Against Cancer-Associated Neuropathic Pain: Effects on Prostate Cancer Progression in an <i>In Vivo</i> Rat Model, BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY, Vol: 118, Pages: 200-207, ISSN: 1742-7835
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- Citations: 18
Fraser SP, Hemsley F, Djamgoz MBA, 2016, Caffeic acid phenethyl ester: Inhibition of metastatic cell behaviours <i>via</i> voltage-gated sodium channel in human breast cancer <i>in vitro</i>, INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY, Vol: 71, Pages: 111-118, ISSN: 1357-2725
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- Citations: 26
Djamgoz MBA, 2015, Blood pressure and risk of cancer progression - A possible connection with salt and voltage-gated sodium channel, MEDICAL HYPOTHESES, Vol: 85, Pages: 591-593, ISSN: 0306-9877
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- Citations: 7
Fraser SP, Foo I, Djamgoz MBA, 2015, Local anaesthetic use in cancer surgery and disease recurrence: role of voltage-gated sodium channels? (vol 113, pg 899, 2015), BRITISH JOURNAL OF ANAESTHESIA, Vol: 114, Pages: 1014-1014, ISSN: 0007-0912
Fraser SP, Foo I, Djamgoz MBA, 2014, Local anaesthetic use in cancer surgery and disease recurrence: role of voltage-gated sodium channels?, BRITISH JOURNAL OF ANAESTHESIA, Vol: 113, Pages: 899-902, ISSN: 0007-0912
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- Citations: 28
Fraser SP, Ozerlat-Gunduz I, Brackenbury WJ, et al., 2014, Regulation of voltage-gated sodium channel expression in cancer: hormones, growth factors and auto-regulation, PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES, Vol: 369, ISSN: 0962-8436
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- Citations: 98
Djamgoz MBA, Coombes RC, Schwab A, 2014, Ion transport and cancer: from initiation to metastasis Introduction, PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES, Vol: 369, ISSN: 0962-8436
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- Citations: 64
Lee SK, Dawson J, Lee JA, et al., 2014, Management of cancer pain: 1. Wider implications of orthodox analgesics., Int J Gen Med, Vol: 7, Pages: 49-58, ISSN: 1178-7074
In this review, the first of two parts, we first provide an overview of the orthodox analgesics used commonly against cancer pain. Then, we examine in more detail the emerging evidence for the potential impact of analgesic use on cancer risk and disease progression. Increasing findings suggest that long-term use of nonsteroidal anti-inflammatory drugs, particularly aspirin, may reduce cancer occurrence. However, acetaminophen may raise the risk of some hematological malignancies. Drugs acting upon receptors of gamma-aminobutyric acid (GABA) and GABA "mimetics" (eg, gabapentin) appear generally safe for cancer patients, but there is some evidence of potential carcinogenicity. Some barbiturates appear to slightly raise cancer risks and can affect cancer cell behavior in vitro. For cannabis, studies suggest an increased risk of squamous cell carcinoma of the tongue, larynx, and possibly lung. Morphine may stimulate human microvascular endothelial cell proliferation and angiogenesis; it is not clear whether this might cause harm or produce benefit. The opioid, fentanyl, may promote growth in some tumor cell lines. Opium itself is an emerging risk factor for gastric adenocarcinoma and possibly cancers of the esophagus, bladder, larynx, and lung. It is concluded that analgesics currently prescribed for cancer pain can significantly affect the cancer process itself. More futuristically, several ion channels are being targeted with novel analgesics, but many of these are also involved in primary and/or secondary tumorigenesis. Further studies are needed to elucidate possible cellular and molecular effects of orthodox analgesics and their possible long-term impact, both positive and negative, and thus enable the best possible clinical gain for cancer patients.
Fraser SP, Peters A, Fleming-Jones S, et al., 2014, Resveratrol: Inhibitory Effects on Metastatic Cell Behaviors and Voltage-Gated Na<SUP>+</SUP> Channel Activity in Rat Prostate Cancer In Vitro, NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL, Vol: 66, Pages: 1047-1058, ISSN: 0163-5581
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- Citations: 22
Frede J, Fraser SP, Oskay-Oezcelik G, et al., 2013, Ovarian cancer: Ion channel and aquaporin expression as novel targets of clinical potential, EUROPEAN JOURNAL OF CANCER, Vol: 49, Pages: 2331-2344, ISSN: 0959-8049
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- Citations: 52
Djamgoz MBA, Onkal R, 2013, Persistent Current Blockers of Voltage-Gated Sodium Channels: A Clinical Opportunity for Controlling Metastatic Disease, RECENT PATENTS ON ANTI-CANCER DRUG DISCOVERY, Vol: 8, Pages: 66-84, ISSN: 1574-8928
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- Citations: 82
Mokhtar NF, Djamgoz MBA, 2012, Voltage-gated Sodium Channel as Potential Target for Metastatic Breast Cancer: Anti-invasive Effects of Commonly Used Blockers, 24th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics, Publisher: ELSEVIER SCI LTD, Pages: 154-155, ISSN: 0959-8049
Yildirim S, Altun S, Gumushan H, et al., 2012, Voltage-gated sodium channel activity promotes prostate cancer metastasis <i>in vivo</i>, CANCER LETTERS, Vol: 323, Pages: 58-61, ISSN: 0304-3835
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- Citations: 76
Batcioglu K, Uyumlu AB, Satilmis B, et al., 2012, Oxidative Stress in the in vivo DMBA Rat Model of Breast Cancer: Suppression by a Voltage-gated Sodium Channel Inhibitor (RS100642), BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY, Vol: 111, Pages: 137-141, ISSN: 1742-7835
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- Citations: 40
McKinlay R, Dassyne J, Djamgoz M, et al., 2012, Agricultural pesticides and chemical fertilisers, Pollutants, Human Health and the Environment: A Risk Based Approach, Editors: Plant, Voulvoulis, Ragnarsdottir, Chichester, Publisher: Wiley-Blackwell
Andrikopoulos P, Baba A, Matsuda T, et al., 2011, Ca<SUP>2+</SUP> Influx through Reverse Mode Na<SUP>+</SUP>/Ca<SUP>2+</SUP> Exchange Is Critical for Vascular Endothelial Growth Factor-mediated Extracellular Signal-regulated Kinase (ERK) 1/2 Activation and Angiogenic Functions of Human Endothelial Cells, JOURNAL OF BIOLOGICAL CHEMISTRY, Vol: 286, Pages: 37919-37931, ISSN: 0021-9258
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- Citations: 62
Bee A, Brewer D, Beesley C, et al., 2011, siRNA Knockdown of Ribosomal Protein Gene RPL19 Abrogates the Aggressive Phenotype of Human Prostate Cancer, PLOS ONE, Vol: 6, ISSN: 1932-6203
We provide novel functional data that posttranscriptional silencing of gene RPL19 using RNAi not only abrogates the malignant phenotype of PC-3M prostate cancer cells but is selective with respect to transcription and translation of other genes. Reducing RPL19 transcription modulates a subset of genes, evidenced by gene expression array analysis and Western blotting, but does not compromise cell proliferation or apoptosis in-vitro. However, growth of xenografted tumors containing the knocked-down RPL19 in-vivo is significantly reduced. Analysis of the modulated genes reveals induction of the non-malignant phenotype principally to involve perturbation of networks of transcription factors and cellular adhesion genes. The data provide evidence that extra-ribosomal regulatory functions of RPL19, beyond protein synthesis, are critical regulators of cellular phenotype. Targeting key members of affected networks identified by gene expression analysis raises the possibility of therapeutically stabilizing a benign phenotype generated by modulating the expression of an individual gene and thereafter constraining a malignant phenotype while leaving non-malignant tissues unaffected.
Andrikopoulos P, Fraser SP, Patterson L, et al., 2011, Angiogenic Functions of Voltage-gated Na<SUP>+</SUP> Channels in Human Endothelial Cells <i>MODULATION OF VASCULAR ENDOTHELIAL GROWTH FACTOR</i> (<i>VEGF</i>) <i>SIGNALING</i>, JOURNAL OF BIOLOGICAL CHEMISTRY, Vol: 286, Pages: 16846-16860, ISSN: 0021-9258
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- Citations: 80
Akum ME, Yamaci RF, Charalambous C, et al., 2011, The Distribution of Carcinogenic Heavy Metals in Cyprus Soil, International Conference on Environment: Survival and Sustainability, Publisher: SPRINGER-VERLAG BERLIN, Pages: 353-359, ISSN: 2199-9155
Djamgoz MBA, 2011, Bioelectricty of Cancer <i>Voltage</i>-<i>Gated Ion Channels and Direct</i>-<i>Current Electric Fields</i>, PHYSIOLOGY OF BIOELECTRICITY IN DEVELOPMENT, TISSUE REGENERATION, AND CANCER, Editors: Pullar, Publisher: CRC PRESS-TAYLOR & FRANCIS GROUP, Pages: 267-292, ISBN: 978-1-4398-3723-8
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- Citations: 9
Schwab A, Stock C, Swietach P, et al., 2010, Ion transport proteins control pancreatic ductal adenocarcinoma, ONKOLOGIE, Vol: 33, Pages: 269-269, ISSN: 0378-584X
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- Citations: 1
Fraser SP, Ozerlat-Gunduz I, Onkal R, et al., 2010, Estrogen and Non-Genomic Upregulation of Voltage-Gated Na<SUP>+</SUP> Channel Activity in MDA-MB-231 Human Breast Cancer Cells: Role in Adhesion, JOURNAL OF CELLULAR PHYSIOLOGY, Vol: 224, Pages: 527-539, ISSN: 0021-9541
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- Citations: 37
Mazurek MP, Prasad PD, Gopal E, et al., 2010, Molecular origin of plasma membrane citrate transporter in human prostate epithelial cells, EMBO REPORTS, Vol: 11, Pages: 431-437, ISSN: 1469-221X
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- Citations: 30
Yao S, Bee A, Brewer D, et al., 2010, PRKC-ζ Expression Promotes the Aggressive Phenotype of Human Prostate Cancer Cells and Is a Novel Target for Therapeutic Intervention., Genes Cancer, Vol: 1, Pages: 444-464
We show protein kinase C-zeta (PKC-ζ) to be a novel predictive biomarker for survival from prostate cancer (P < 0.001). We also confirm that transcription of the PRKC-ζ gene is crucial to the malignant phenotype of human prostate cancer. Following siRNA silencing of PRKC-ζ in PC3-M prostate cancer cells, stable transfectant cell line si-PRKC-ζ-PC3-M(T1-6) is phenotypically nonmalignant in vitro and in vivo. Genome-wide expression analysis identified 373 genes to be differentially expressed in the knockdown cells and 4 key gene networks to be significantly perturbed during phenotype modulation. Functional interconnection between some of the modulated genes is revealed, although these may be within different regulatory pathways, emphasizing the complexity of their mutual interdependence. Genes with altered expression following PRKC-ζ knockdown include HSPB1, RAD51, and ID1 that we have previously described to be critical in prostatic malignancy. Because expression of PRKC-ζ is functionally involved in promoting the malignant phenotype, we propose PKC-ζ as a novel and biologically relevant target for therapeutic intervention in prostate cancer.
Djamgoz MB, Onkal R, 2010, Electrophysiological Characteristics of Neonatal Nav1.5 Expressed in a Highly Invasive Human Breast Cancer Cell Line: Sensitivity to pH and Divalent Cations, BIOPHYSICAL JOURNAL, Vol: 98, Pages: 310A-310A, ISSN: 0006-3495
Chioni AM, Shao D, Grose R, et al., 2010, Protein kinase A and regulation of neonatal Nav1.5 expression in human breast cancer cells: activity-dependent positive feedback and cellular migration, Int J Biochem Cell Biol, Vol: 42, Pages: 346-358, ISSN: 1878-5875
Voltage-gated Na(+) channels (VGSCs) are expressed in excitable cells (e.g. neurons and muscles), as well as in some classically 'non-excitable' cells (e.g. fibroblasts), and in carcinomas. In general, functional expression of VGSCs in plasma membrane (PM) is hierarchical and dynamic. Previously, we have shown that an activity-dependent positive feedback mechanism involving cAMP-dependent protein kinase A (PKA) plays a significant role in upregulation of VGSCs in strongly metastatic rat prostate cancer Mat-LyLu cells expressing Nav1.7. Here, we investigated the possible role of PKA in VGSC regulation and its functional consequences in strongly metastatic human breast cancer (BCa) MDA-MB-231 cells, where the neonatal splice form of Nav1.5 (nNav1.5) is the predominant VGSC present. Treatment with the PKA activator forskolin for 24h increased mRNA and PM protein levels of nNav1.5, without changing the total VGSC protein level. Opposite effects were obtained by application of the PKA inhibitor KT5720 or the highly specific VGSC blocker tetrodotoxin (TTX), the latter implying activity-dependent upregulation. We tested the possibility, therefore, that the activity dependence of VGSC (nNav1.5) expression involved PKA. Indeed, TTX pretreatment reduced the level of phosphorylated PKA and eliminated basal and PKA-stimulated cellular migration. These data suggested that activity-dependent positive feedback mediated by PKA plays an important role in the functional expression of nNav1.5 in BCa, and in turn, this enhances the cells' metastatic potential.
Onkal R, Djamgoz MBA, 2009, Molecular pharmacology of voltage-gated sodium channel expression in metastatic disease: Clinical potential of neonatal Nav1.5 in breast cancer, EUROPEAN JOURNAL OF PHARMACOLOGY, Vol: 625, Pages: 206-219, ISSN: 0014-2999
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- Citations: 97
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