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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
#1
Junhao Huang, Hideki Furuya, Malika Faouzi, Zheng Zhang, Mahealani Monteilh-Zoller, F Kelly Galbraith Kawabata, 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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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-imidazo-1-2-a-pyridine-series-of-autotaxin-inhibitors
#9
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, 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 co-crystal 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...
July 21, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28725634/ip3-receptor-mediated-calcium-signaling-and-its-role-in-autophagy-in-cancer
#10
REVIEW
Elzbieta Kania, Gemma Roest, Tim Vervliet, Jan B Parys, Geert Bultynck
Calcium ions (Ca(2+)) play a complex role in orchestrating diverse cellular processes, including cell death and survival. To trigger signaling cascades, intracellular Ca(2+) is shuffled between the cytoplasm and the major Ca(2+) stores, the endoplasmic reticulum (ER), the mitochondria, and the lysosomes. A key role in the control of Ca(2+) signals is attributed to the inositol 1,4,5-trisphosphate (IP3) receptors (IP3Rs), the main Ca(2+)-release channels in the ER. IP3Rs can transfer Ca(2+) to the mitochondria, thereby not only stimulating core metabolic pathways but also increasing apoptosis sensitivity and inhibiting basal autophagy...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28723646/collagen-type-1-promotes-survival-of-human-breast-cancer-cells-by-overexpressing-kv10-1-potassium-and-orai1-calcium-channels-through-ddr1-dependent-pathway
#11
Mehdi Badaoui, Cloé Mimsy-Julienne, Charles Saby, Laurence Van Gulick, Marta Peretti, Pierre Jeannesson, Hamid Morjani, Halima Ouadid-Ahidouch
Collagen type 1 is among the tumor microenvironment (TM) factors, that regulates proliferation, survival, migration and invasion. Ion channels are key players in interactions between tumor cells and TM. Kv10.1 has been shown to play an essential role in breast cancer cell proliferation and migration by permitting Ca2+ influx notably via Orai1. Here, we show that human breast cancer (BC) cells growing, in culture media completely devoid of the serum and seeded on collagen 1 coating, exhibited less apoptotic rate and a decrease in Bax expression when compared to those grown on plastic...
July 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28720769/concentration-dependent-binding-of-small-ligands-to-multiple-saturable-sites-in-membrane-proteins
#12
Letícia Stock, Juliana Hosoume, Werner Treptow
Membrane proteins are primary targets for most therapeutic indications in cancer and neurological diseases, binding over 50% of all known small molecule drugs. Understanding how such ligands impact membrane proteins requires knowledge on the molecular structure of ligand binding, a reasoning that has driven relentless efforts in drug discovery and translational research. Binding of small ligands appears however highly complex involving interaction to multiple transmembrane protein sites featuring single or multiple occupancy states...
July 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28713289/mitochondrial-vdac1-a-key-gatekeeper-as-potential-therapeutic-target
#13
REVIEW
Amadou K S Camara, YiFan Zhou, Po-Chao Wen, Emad Tajkhorshid, Wai-Meng Kwok
Mitochondria are the key source of ATP that fuels cellular functions, and they are also central in cellular signaling, cell division and apoptosis. Dysfunction of mitochondria has been implicated in a wide range of diseases, including neurodegenerative and cardiac diseases, and various types of cancer. One of the key proteins that regulate mitochondrial function is the voltage-dependent anion channel 1 (VDAC1), the most abundant protein on the outer membrane of mitochondria. VDAC1 is the gatekeeper for the passages of metabolites, nucleotides, and ions; it plays a crucial role in regulating apoptosis due to its interaction with apoptotic and anti-apoptotic proteins, namely members of the Bcl-2 family of proteins and hexokinase...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28708947/kv10-1-potassium-channel-from-the-brain-to-the-tumors
#14
Verna Cázares-Ordoñez, Luis A Pardo
<i>KCNH1</i> gene encodes the Kv10.1 (Eag1) ion channel, a member of the EAG (ether-à-go-go) family of voltage-gated potassium channels. Recent studies have demonstrated that <i>KCHN1</i> mutations are implicated in Temple-Baraitser and Zimmermann-Laband syndromes and other forms of developmental deficits that all present with mental retardation and epilepsy, suggesting that Kv10.1 might be important for cognitive development in human. Although Kv10.1 channel is mainly expressed in the mammalian brain, its ectopic expression occurs in 70% of human cancers...
July 14, 2017: Biochemistry and Cell Biology, Biochimie et Biologie Cellulaire
https://www.readbyqxmd.com/read/28698214/papers-of-note-in-nature547-7661
#15
Annalisa M VanHook
This week's articles highlight progress in predicting T cell receptor specificity; an evolutionarily ancient form of antiviral defense; a mechanism of chemotherapy-induced cell death; metabolic rewiring in cancer cells; and structural insights into activation of a GPCR and of a mechanosensitive ion channel.
July 11, 2017: Science Signaling
https://www.readbyqxmd.com/read/28693898/nanosecond-pulsed-electric-fields-depolarize-transmembrane-potential-via-voltage-gated-k-ca-2-and-trpm8-channels-in-u87-glioblastoma-cells
#16
Ryan C Burke, Sylvia M Bardet, Lynn Carr, Sergii Romanenko, Delia Arnaud-Cormos, Philippe Leveque, Rodney P O'Connor
Nanosecond pulsed electric fields (nsPEFs) have a variety of applications in the biomedical and biotechnology industries. Cancer treatment has been at the forefront of investigations thus far as nsPEFs permeabilize cellular and intracellular membranes leading to apoptosis and necrosis. nsPEFs may also influence ion channel gating and have the potential to modulate cell physiology without poration of the membrane. This phenomenon was explored using live cell imaging and a sensitive fluorescent probe of transmembrane voltage in the human glioblastoma cell line, U87 MG, known to express a number of voltage-gated ion channels...
July 8, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28679281/lipid-mediated-modulation-of-intracellular-ion-channels-and-redox-state-physio-pathological-implications
#17
Marisa Brini, Luigi Leanza, Ildiko Szabo
<i>Significance</i>: Ion channels play an important role in the regulation of organelle function within the cell, as proven by increasing evidence pointing to a link between altered function of intracellular ion channels and different pathologies ranging from cancer to neurodegenerative diseases, ischemic damage and lysosomal storage diseases. <i>Recent Advances</i>: A link between these pathologies and redox state as well as lipid homeostasis and ion channel function is in the focus of current research...
July 5, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28659615/kca3-1-activation-via-p2y2-purinergic-receptors-promotes-human-ovarian-cancer-cell-skov-3-migration
#18
L Robles-Martínez, E Garay, M G Martel-Gallegos, A Cisneros-Mejorado, D Pérez-Montiel, A Lara, R O Arellano
Disorders in cell signaling mediated by ATP or histamine, activating specific membrane receptors, have been frequently associated with tumorigenesis. Among the elements of response to purinergic (and histaminergic) signaling, ion channel activation controls essential cellular processes in cancer, such as cell proliferation, motility, and death. Here, we studied the effects that ATP had on electrical properties of human ovarian adenocarcinoma cells named SKOV-3. ATP caused increase in intracellular Ca(2+) concentration ([Ca(2+)]i) and, concurrently, it evoked a complex electrical response with a conspicuous outward component...
June 28, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28626428/molecular-surgery-concept-from-bench-to-bedside-a-focus-on-trpv1-pain-sensing-neurons
#19
REVIEW
László Pecze, Béla Viskolcz, Zoltán Oláh
"Molecular neurosurgery" is emerging as a new medical concept, and is the combination of two partners: (i) a molecular neurosurgery agent, and (ii) the cognate receptor whose activation results in the selective elimination of a specific subset of neurons in which this receptor is endogenously expressed. In general, a molecular surgery agent is a selective and potent ligand, and the target is a specific cell type whose elimination is desired through the molecular surgery procedure. These target cells have the highest innate sensitivity to the molecular surgery agent usually due to the highest receptor density being in their plasma membrane...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28618956/acid-sensing-ion-channels-contribute-to-the-effect-of-extracellular-acidosis-on-proliferation-and-migration-of-a549-cells
#20
Yu Wu, Bo Gao, Qiu-Ju Xiong, Yu-Chan Wang, Da-Ke Huang, Wen-Ning Wu
Acid-sensing ion channels, a proton-gated cation channel, can be activated by low extracellular pH and involved in pathogenesis of some tumors such as glioma and breast cancer. However, the role of acid-sensing ion channels in the growth of lung cancer cell is unclear. In this study, we investigated the expression of acid-sensing ion channels in human lung cancer cell line A549 and their possible role in proliferation and migration of A549 cells. The results show that acid-sensing ion channel 1, acid-sensing ion channel 2, and acid-sensing ion channel 3 are expressed in A549 cells at the messenger RNA and protein levels, and acid-sensing ion channel-like currents were elicited by extracellular acid stimuli...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
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