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https://www.readbyqxmd.com/read/28927426/the-acid-sensing-ion-channel-asic2-promotes-invasion-and-metastasis-of-colorectal-cancer-under-acidosis-by-activating-the-calcineurin-nfat1-axis
#1
Zhi-Hang Zhou, Jin-Wen Song, Wen Li, Xue Liu, Liu Cao, Lu-Ming Wan, Ying-Xia Tan, Shou-Ping Ji, Yu-Mei Liang, Feng Gong
BACKGROUND: The tumor acidic microenvironment, a common biochemical event in solid tumors, offers evolutional advantage for tumors cells and even enhances their aggressive phenotype. However, little is known about the molecular mechanism underlying the acidic microenvironment-induced invasion and metastasis. METHODS: We examined the expression of the acid-sending ion channel (ASIC) family members after acidic exposure using RT-PCR and immunofluoresence. Gene manipulation was applied to reveal the potential of ASIC2 on invasion, proliferation, colony formation of colorectal cancer (CRC)...
September 19, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28923947/tpc2-polymorphisms-associated-with-a-hair-pigmentation-phenotype-in-humans-result-in-gain-of-channel-function-by-independent-mechanisms
#2
Yu-Kai Chao, Verena Schludi, Cheng-Chang Chen, Elisabeth Butz, O N Phuong Nguyen, Martin Müller, Jens Krüger, Claudia Kammerbauer, Manu Ben-Johny, Angelika M Vollmar, Carola Berking, Martin Biel, Christian A Wahl-Schott, Christian Grimm
Two-pore channels (TPCs) are endolysosomal cation channels. Two members exist in humans, TPC1 and TPC2. Functional roles associated with the ubiquitously expressed TPCs include VEGF-induced neoangiogenesis, LDL-cholesterol trafficking and degradation, physical endurance under fasting conditions, autophagy regulation, the acrosome reaction in sperm, cancer cell migration, and intracellular trafficking of pathogens such as Ebola virus or bacterial toxins (e.g., cholera toxin). In a genome-wide association study for variants associated with human pigmentation characteristics two coding variants of TPC2, rs35264875 (encoding M484L) and rs3829241 (encoding G734E), have been found to be associated with a shift from brown to blond hair color...
September 18, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28913175/regulation-of-endoplasmic-reticulum-mitochondria-ca-2-transfer-and-its-importance-for-anti-cancer-therapies
#3
REVIEW
Gaia Pedriali, Alessandro Rimessi, Luigi Sbano, Carlotta Giorgi, Mariusz R Wieckowski, Maurizio Previati, Paolo Pinton
Inter-organelle membrane contact sites are emerging as major sites for the regulation of intracellular Ca(2+) concentration and distribution. Here, extracellular stimuli operate on a wide array of channels, pumps, and ion exchangers to redistribute intracellular Ca(2+) among several compartments. The resulting highly defined spatial and temporal patterns of Ca(2+) movement can be used to elicit specific cellular responses, including cell proliferation, migration, or death. Plasma membrane (PM) also can directly contact mitochondria and endoplasmic reticulum (ER) through caveolae, small invaginations of the PM that ensure inter-organelle contacts, and can contribute to the regulation of numerous cellular functions through scaffolding proteins such as caveolins...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28902151/apetx4-a-novel-sea-anemone-toxin-and-a-modulator-of-the-cancer-relevant-potassium-channel-kv10-1
#4
Lien Moreels, Steve Peigneur, Diogo T Galan, Edwin De Pauw, Lászlo Béress, Etienne Waelkens, Luis A Pardo, Loïc Quinton, Jan Tytgat
The human ether-à-go-go channel (hEag1 or KV10.1) is a cancer-relevant voltage-gated potassium channel that is overexpressed in a majority of human tumors. Peptides that are able to selectively inhibit this channel can be lead compounds in the search for new anticancer drugs. Here, we report the activity-guided purification and electrophysiological characterization of a novel KV10.1 inhibitor from the sea anemone Anthopleura elegantissima. Purified sea anemone fractions were screened for inhibitory activity on KV10...
September 13, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28901280/neuronal-and-extraneuronal-nicotinic-acetylcholine-receptors
#5
Michele Zoli, Susanna Pucci, Antonietta Vilella, Cecilia Gotti
Neuronal nicotinic acetylcholine receptors (nAChRs) belong to a super-family of Cys-loop ligand-gated ion channels that respond to endogenous acetylcholine (ACh) or other cholinergic ligands. These receptors are also the targets of drugs such as nicotine (the main addictive agent delivered by cigarette smoke) and are involved in a variety of physiological and pathophysiological processes. Numerous studies have shown that the expression and/or function of nAChRs is compromised in many neurological and psychiatric diseases...
September 11, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28901272/disorders-of-mechanisms-of-calcium-metabolism-control-as-potential-risk-factors-of-prostate-cancer
#6
Dorota Skrajnowska, Barbara Bobrowska-Korczak, Andrzej Tokarz
Prostate cancer significantly affects the overall morbidity and mortality of malignant tumours in highly developed countries. Important risk factors include family predisposition and regional, racial and dietary determinants. The scientific literature contains a great deal of data on the role of calcium and dairy products in general in the process of neoplastic transformation of the prostate. This is most likely linked to the fact that changes in the concentration of calcium ions control such varied life processes as secretion of hormones and neurotransmitters, the level of cyclic nucleotides, and cell growth, division and differentiation...
September 12, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28899508/pellitorine-an-extract-of-tetradium-daniellii-is-an-antagonist-of-the-ion-channel-trpv1
#7
Zoltán Oláh, Dóra Rédei, László Pecze, Csaba Vizler, Katalin Jósvay, Péter Forgó, Zoltán Winter, György Dombi, Gerda Szakonyi, Judit Hohmann
BACKGROUND: Transient Receptor Potential Vanilloid 1 (TRPV1) confers noxious heat and inflammatory pain signals in the peripheral nervous system. Clinical trial of resiniferatoxin from Euphorbia species is successfully aimed at TRPV1 in cancer pain management and heading toward new selective painkiller status that further validates this target for drug discovery efforts. Evodia species, used in traditional medicine for hundreds of years, are a recognised source of different TRPV1 agonists, but no antagonist has yet been reported...
October 15, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/28883041/normoxic-cells-remotely-regulate-the-acid-base-balance-of-cells-at-the-hypoxic-core-of-connexin-coupled-tumor-growths
#8
Tobias H Dovmark, Alzbeta Hulikova, Steven A Niederer, Richard D Vaughan-Jones, Pawel Swietach
ATP fuels the removal of metabolic end-products, including H(+) ions that profoundly modulate biological activities. Energetic resources in hypoxic tumor regions are constrained by low-yielding glycolysis, and any means of reducing the cost of acid extrusion, without compromising pH homeostasis, would therefore be advantageous for cancer cells. Some cancers express connexin channels that allow solute exchange between cells, and we propose that, via this route, normoxic cells supply hypoxic neighbors with acid-neutralizing HCO3(-) ions...
September 7, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28877446/role-of-ion-channels-in-natural-killer-cell-function-towards-cancer
#9
John Redmond, Debbie O'Rilley, Paul Buchanan
Progression of cancer to advanced states is associated with treatment resistance and metastatic spread -- features that are linked to poor prognosis and patient mortality. Investigations into potential new treatments to reduce cancer spread are ongoing, with immunotherapy generating much interest. Natural killer (NK) cells are part of the body's innate immune system and are known for their ability to target and lyse cancer cells. Ion channels have previously been linked to the growth and development of tumors, but recent research suggests that these channels may also serve to alter immune cell functioning...
June 2017: Discovery Medicine
https://www.readbyqxmd.com/read/28859093/pulling-mscl-open-via-n-terminal-and-tm1-helices-a-computational-study-towards-engineering-an-mscl-nanovalve
#10
Adam D Martinac, Navid Bavi, Omid Bavi, Boris Martinac
There are great opportunities in the manipulation of bacterial mechanosensitive (MS) ion channels for specific and targeted drug delivery purposes. Recent research has shown that these ion channels have the potential to be converted into nanovalves through clever use of magnetic nanoparticles and magnetic fields. Using a combination of molecular dynamics (MD) simulations and the finite element (FE) modelling, this study investigates the theoretical feasibility of opening the MscL channel (MS channel of large conductance of E...
2017: PloS One
https://www.readbyqxmd.com/read/28857015/n-glycosylation-of-the-transient-receptor-potential-melastatin-8-channel-is-altered-in-pancreatic-cancer-cells
#11
Roxana Ulăreanu, Gabriela Chiriţoiu, Florentina Cojocaru, Alexandru Deftu, Violeta Ristoiu, Luciana Stănică, Dan F Mihăilescu, Dana Cucu
Transient receptor potential melastatin 8 (TRPM8), a membrane ion channel, is activated by thermal and chemical stimuli. In pancreatic ductal adenocarcinoma, TRPM8 is required for cell migration, proliferation, and senescence and is associated with tumor size and pancreatic ductal adenocarcinoma stages. Although the underlying mechanisms of these processes have yet to be described, this cation-permeable channel has been proposed as an oncological target. In this study, the glycosylation status of the TRPM8 channel was shown to affect cell proliferation, cell migration, and calcium uptake...
August 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28810912/inhibition-of-trpm7-suppresses-cell-proliferation-of-colon-adenocarcinoma-in-vitro-and-induces-hypomagnesemia-in-vivo-without-affecting-azoxymethane-induced-early-colon-cancer-in-mice
#12
Junhao Huang, Hideki Furuya, Malika Faouzi, Zheng Zhang, Mahealani Monteilh-Zoller, Kelly Galbraith Kawabata, F David Horgen, Toshihiko Kawamori, Reinhold Penner, Andrea Fleig
BACKGROUND: Magnesium (Mg(2+)) is an essential cation implicated in carcinogenesis, solid tumor progression and metastatic potential. The Transient Receptor Potential Melastatin Member 7 (TRPM7) is a divalent ion channel involved in cellular and systemic Mg(2+) homeostasis. Abnormal expression of TRPM7 is found in numerous cancers, including colon, implicating TRPM7 in this process. METHODS: To establish a possible link between systemic magnesium (Mg(2+)) status, the Mg(2+) conducting channel TRPM7 in colon epithelial cells, and colon carcinogenesis, in vitro whole-cell patch clamp electrophysiology, qPCR, and pharmacological tools were used probing human colorectal adenocarcinoma HT-29 as well as normal primary mouse colon epithelial cells...
August 15, 2017: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/28806761/transcriptome-analysis-of-pdgfr%C3%AE-cells-identifies-t-type-ca2-channel-cacna1g-as-a-new-pathological-marker-for-pdgfr%C3%AE-cell-hyperplasia
#13
Se Eun Ha, Moon Young Lee, Masaaki Kurahashi, Lai Wei, Brian G Jorgensen, Chanjae Park, Paul J Park, Doug Redelman, Kent C Sasse, Laren S Becker, Kenton M Sanders, Seungil Ro
Platelet-derived growth factor receptor alpha (PDGFRα)+ cells are distributed into distinct morphological groups within the serosal, muscular, and submucosal layers as well as the myenteric and deep muscular plexi. PDGFRα+ cells directly interact with interstitial cells of Cajal (ICC) and smooth muscle cells (SMC) in gastrointestinal smooth muscle tissue. These three cell types, SMC, ICC, and PDGFRα+ cells (SIP cells), form an electrical syncytium, which dynamically regulates gastrointestinal motility. We have previously reported the transcriptomes of SMC and ICC...
2017: PloS One
https://www.readbyqxmd.com/read/28795251/5-fluorouracil-induced-mitochondrial-oxidative-cytotoxicity-and-apoptosis-are-increased-in-mcf-7-human-breast-cancer-cells-by-trpv1-channel-activation-but-not-hypericum-perforatum-treatment
#14
Haci Ahmet Deveci, Mustafa Nazıroğlu, Gökhan Nur
5-Fluorouracil (5-FU) is a widely used chemotherapy agent for breast cancer, although drug resistance is a critical issue regarding the use of this agent in the disease. Calcium signaling is a well-known main cause of proliferation and apoptosis in breast cancer cells. Although previous studies have implicated TRPV1 inhibitor, anticancer, and apoptotic roles of Hypericum perforatum (HPer) in several cells, the synergistic inhibition effects of HPer and 5-FU in cancer and the stimulation of ongoing apoptosis have not yet been clarified in MCF-7 cells...
August 9, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28783331/discovery-and-synthesis-of-caracolamide-a-an-ion-channel-modulating-dichlorovinylidene-containing-phenethylamide-from-a-panamanian-marine-cyanobacterium-cf-symploca-species
#15
C Benjamin Naman, Jehad Almaliti, Lorene Armstrong, Eduardo J Caro-Díaz, Marsha L Pierce, Evgenia Glukhov, Amanda Fenner, Carmenza Spadafora, Hosana M Debonsi, Pieter C Dorrestein, Thomas F Murray, William H Gerwick
A recent untargeted metabolomics investigation into the chemical profile of 10 organic extracts from cf. Symploca spp. revealed several interesting chemical leads for further natural product drug discovery. Subsequent target-directed isolation efforts with one of these, a Panamanian marine cyanobacterium cf. Symploca sp., yielded a phenethylamide metabolite that terminates in a relatively rare gem-dichlorovinylidene moiety, caracolamide A (1), along with a known isotactic polymethoxy-1-alkene (2). Detailed NMR and HRESIMS analyses were used to determine the structures of these molecules, and compound 1 was confirmed by a three-step synthesis...
August 7, 2017: Journal of Natural Products
https://www.readbyqxmd.com/read/28781795/transmembrane-channel-like-protein-8-as-a-potential-biomarker-for-poor-prognosis-of-hepatocellular-carcinoma
#16
Panpan Lu, Qiang Ding, Shuping Ding, Yuhui Fan, Xin Li, Dean Tian, Mei Liu
Hepatocellular carcinoma (HCC) is an aggressive malignant tumor and the third leading cause of cancer-related mortality worldwide. Transmembrane channel-like protein 8 (TMC8) is reported to play a major role in several aspects of human pathophysiology, such as ion channel permeability, human papillomavirus infection and skin cancer; however, its role in HCC has not been fully elucidated. The aim of the present study was to investigate the expression levels of TMC8 in 146 pairs of liver cancer samples and adjacent non-tumorous samples using immunohistochemistry...
August 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28776687/mesenchymal-stem-cell-differentiation-control-by-calcium-activated-potassium-channels
#17
REVIEW
Ekaterina Pchelintseva, Mustafa B A Djamgoz
Mesenchymal stem cells (MSCs) are widely used in modern medicine for which understanding the mechanisms controlling their differentiation is fundamental. Ion channels offer novel insights to this process because of their role in modulating membrane potential and intracellular milieu. Here, we evaluate the contribution of calcium-activated potassium (KCa ) channels to the three main components of MSC differentiation: initiation, proliferation, and migration. First, we demonstrate the importance of the membrane potential (Vm ) and the apparent association of hyperpolarization with differentiation...
August 4, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28759041/oncosis-and-apoptosis-induction-by-activation-of-an-overexpressed-ion-channel-in-breast-cancer-cells
#18
A A Peters, S Y N Jamaludin, K T D S Yapa, S Chalmers, A P Wiegmans, H F Lim, M J G Milevskiy, I Azimi, F M Davis, K S Northwood, E Pera, D L Marcial, E Dray, N J Waterhouse, P J Cabot, T J Gonda, P A Kenny, M A Brown, K K Khanna, S J Roberts-Thomson, G R Monteith
The critical role of calcium signalling in processes related to cancer cell proliferation and invasion has seen a focus on pharmacological inhibition of overexpressed ion channels in specific cancer subtypes as a potential therapeutic approach. However, despite the critical role of calcium in cell death pathways, pharmacological activation of overexpressed ion channels has not been extensively evaluated in breast cancer. Here we define the overexpression of transient receptor potential vanilloid 4 (TRPV4) in a subgroup of breast cancers of the basal molecular subtype...
July 31, 2017: Oncogene
https://www.readbyqxmd.com/read/28752501/prognostic-value-of-ion-channel-genes-in-chinese-patients-with-gliomas-based-on-mrna-expression-profiling
#19
Feng-Fei Lu, Hao-Yuan Wang, Xiao-Zheng He, Ting-Yu Liang, Wen Wang, Hui-Min Hu, Fan Wu, Yan-Wei Liu, Shi-Zhong Zhang
Increasing evidence suggests that ion channels not only regulate electric signaling in excitable cells but also play important roles in the development of human cancer. However, the roles of ion channels in glioma remain controversial. We systematically analyzed the expression patterns of ion channel genes in a cohort of Chinese patients with glioma using whole-genome mRNA expression profiling. First, a molecular signature comprising 47 ion channel genes (IC47) was identified using Spearman's rank correlation test conducted between tumor grade and gene expression...
July 27, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28731719/discovery-structure-activity-relationship-and-binding-mode-of-an-imidazo-1-2-a-pyridine-series-of-autotaxin-inhibitors
#20
Agnès Joncour, Nicolas Desroy, Christopher Housseman, Xavier Bock, Natacha Bienvenu, Laëtitia Cherel, Virginie Labeguere, Christophe Peixoto, Denis Annoot, Luce Lepissier, Jörg Heiermann, Willem Jan Hengeveld, Gregor Pilzak, Alain Monjardet, Emanuelle Wakselman, Veronique Roncoroni, Sandrine Le Tallec, René Galien, Christelle David, Nele Vandervoort, Thierry Christophe, Katja Conrath, Mia Jans, Alexandre Wohlkonig, Sameh Soror, Jan Steyaert, Robert Touitou, Damien Fleury, Lionel Vercheval, Patrick Mollat, Nicolas Triballeau, Ellen van der Aar, Reginald Brys, Bertrand Heckmann
Autotaxin (ATX) is a secreted enzyme playing a major role in the production of lysophosphatidic acid (LPA) in blood through hydrolysis of lysophosphatidyl choline (LPC). The ATX-LPA signaling axis arouses a high interest in the drug discovery industry as it has been implicated in several diseases including cancer, fibrotic diseases, and inflammation, among others. An imidazo[1,2-a]pyridine series of ATX inhibitors was identified out of a high-throughput screening (HTS). A cocrystal structure with one of these compounds and ATX revealed a novel binding mode with occupancy of the hydrophobic pocket and channel of ATX but no interaction with zinc ions of the catalytic site...
August 18, 2017: Journal of Medicinal Chemistry
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