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https://www.readbyqxmd.com/read/28518134/asic1-and-asic3-contribute-to-acidity-induced-emt-of-pancreatic-cancer-through-activating-ca-2-rhoa-pathway
#1
Shuai Zhu, Hai-Yun Zhou, Shi-Chang Deng, Shi-Jiang Deng, Chi He, Xiang Li, Jing-Yuan Chen, Yan Jin, Zhuang-Li Hu, Fang Wang, Chun-You Wang, Gang Zhao
Extracellular acid can have important effects on cancer cells. Acid-sensing ion channels (ASICs), which emerged as key receptors for extracellular acidic pH, are differently expressed during various diseases and have been implicated in underlying pathogenesis. This study reports that ASIC1 and ASIC3 are mainly expressed on membrane of pancreatic cancer cells and upregulated in pancreatic cancer tissues. ASIC1 and ASIC3 are responsible for an acidity-induced inward current, which is required for elevation of intracellular Ca(2+) concentration ([Ca(2+)]i)...
May 18, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28480765/targeting-dorsal-root-ganglia-and-primary-sensory-neurons-for-the-treatment-of-chronic-pain
#2
Temugin Berta, Yawar Qadri, Ping-Heng Tan, Ru-Rong Ji
Currently the treatment of chronic pain is inadequate and compromised by debilitating central nervous system side effects. Here we discuss new therapeutic strategies that target dorsal root ganglia (DRGs) in the peripheral nervous system for a better and safer treatment of chronic pain. Areas covered: The DRGs contain the cell bodies of primary sensory neurons including nociceptive neurons. After painful injuries, primary sensory neurons demonstrate maladaptive molecular changes in DRG cell bodies and in their axons...
May 8, 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/28472608/epigenetic-regulation-of-voltage-gated-potassium-ion-channel-molecule-kv1-3-in-mechanisms-of-colorectal-cancer
#3
Tao He, Can Wang, Meiying Zhang, Xiaomei Zhang, Shufang Zheng, Enqiang Linghu, Mingzhou Guo
Colorectal cancer (CRC) is among the leading causes of cancer-related death throughout the world. Aberrant expression of voltage-gated potassium ion channel molecule Kv1.3 has been reported in various cancers. To explore the expression and regulation of Kv1.3 in colorectal cancer, 7 colorectal cancer cell lines and 147 cases of primary colorectal cancer were involved in this study. Kv1.3 was expressed in LOVO and SW480 cells and loss of expression was found in RKO, DLD1, SW620, HCT116, and HT29 cells. Complete methylation was found in RKO, DLD1, SW620, HCT116, and HT29 cells, partial methylation was found in LOVO and SW480 cells...
March 2017: Discovery Medicine
https://www.readbyqxmd.com/read/28469007/golgi-anti-apoptotic-protein-a-tale-of-camels-calcium-channels-and-cancer
#4
REVIEW
Guia Carrara, Maddy Parsons, Nuno Saraiva, Geoffrey L Smith
Golgi anti-apoptotic protein (GAAP), also known as transmembrane Bax inhibitor-1 motif-containing 4 (TMBIM4) or Lifeguard 4 (Lfg4), shares remarkable amino acid conservation with orthologues throughout eukaryotes, prokaryotes and some orthopoxviruses, suggesting a highly conserved function. GAAPs regulate Ca(2+) levels and fluxes from the Golgi and endoplasmic reticulum, confer resistance to a broad range of apoptotic stimuli, promote cell adhesion and migration via the activation of store-operated Ca(2+) entry, are essential for the viability of human cells, and affect orthopoxvirus virulence...
May 2017: Open Biology
https://www.readbyqxmd.com/read/28462107/role-of-transient-receptor-potential-melastatin-type-7-channel-in-gastric-cancer
#5
REVIEW
Byung Joo Kim, Chansik Hong
Transient receptor potential (TRP) proteins are a family of ion channels, which are responsible for a wide array of cellular functions. In particular, TRP melastatin type (TRPM) 7 is expressed everywhere and permeable to divalent cations such as Mg(2+) and Ca(2+). It contains a channel and a kinase domain. Recent studies indicate that activation of TRPM7 plays an important role in the growth and survival of gastric cancer cells. In this review, we describe and discuss the findings of recent studies that have provided novel insights of the relation between TRPM7 and gastric cancer...
June 2016: Integr Med Res
https://www.readbyqxmd.com/read/28457591/from-mucolipidosis-type-iv-to-ebola-trpml-and-two-pore-channels-at-the-crossroads-of-endo-lysosomal-trafficking-and-disease
#6
REVIEW
Christian Grimm, Elisabeth Butz, Cheng-Chang Chen, Christian Wahl-Schott, Martin Biel
What do lysosomal storage disorders such as mucolipidosis type IV have in common with Ebola, cancer cell migration, or LDL-cholesterol trafficking? LDL-cholesterol, certain bacterial toxins and viruses, growth factors, receptors, integrins, macromolecules destined for degradation or secretion are all sorted and transported via the endolysosomal system (ES). There are several pathways known in the ES, e.g. the degradation, the recycling, or the retrograde trafficking pathway. The ES comprises early and late endosomes, lysosomes and recycling endosomes as well as autophagosomes and lysosome related organelles...
April 23, 2017: Cell Calcium
https://www.readbyqxmd.com/read/28452148/understanding-structure-function-relationships-of-the-human-neuronal-acetylcholine-receptor-insights-from-the-first-crystal-structures-of-neuronal-subunits
#7
REVIEW
Petros Giastas, Marios Zouridakis, Socrates J Tzartos
Nicotinic acetylcholine receptors (nAChRs) are the best studied members of the superfamily of pentameric ligand-gated ion channels (pLGICs). Neuronal nAChRs regulate neuronal excitability and neurotransmitter release in the nervous system and form either homo- or hetero-pentameric complexes with various combinations among eleven neuronal nAChR subunits (α2-7, α9, α10 and β2-4) known to exist in humans. In addition to their wide distribution in the nervous system, neuronal nAChRs have been also found in immune cells and many peripheral tissues...
April 27, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28448473/transcriptomic-analysis-of-calcium-remodeling-in-colorectal-cancer
#8
Enrique Pérez-Riesgo, Lucía G Gutiérrez, Daniel Ubierna, Alberto Acedo, Mary P Moyer, Lucía Núñez, Carlos Villalobos
Colorectal cancer (CRC) cells undergo the remodeling of intracellular Ca(2+) homeostasis, which contributes to cancer hallmarks such as enhanced proliferation, invasion and survival. Ca(2+) remodeling includes critical changes in store-operated Ca(2+) entry (SOCE) and Ca(2+) store content. Some changes have been investigated at the molecular level. However, since nearly 100 genes are involved in intracellular Ca(2+) transport, a comprehensive view of Ca(2+) remodeling in CRC is lacking. We have used Next Generation Sequencing (NGS) to investigate differences in expression of 77 selected gene transcripts involved in intracellular Ca(2+) transport in CRC...
April 27, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28438053/scorpion-venom-causes-upregulation-of-p53-and-downregulation-of-bcl-xl-and-bid-protein-expression-by-modulating-signaling-proteins-erk-1-2-and-stat3-and-dna-damage-in-breast-and-colorectal-cancer-cell-lines
#9
Abdulrahman Khazim Al-Asmari, Anvarbatcha Riyasdeen, Mozaffarul Islam
Scorpion venoms efficiently block the normal neurotransmitter signaling pathway by prejudicing the ion channel operating mechanism in the body system. Besides its negative effect, venoms also possess some beneficial qualities for humans. They have also been shown to exhibit anticancer properties in various cancer types. This unique property of the venom as an anticancer agent is mainly a result of its role in initiating apoptosis and inhibiting several signaling cascade mechanisms that promote cancer cell proliferation and growth...
April 1, 2017: Integrative Cancer Therapies
https://www.readbyqxmd.com/read/28426996/design-synthesis-sar-discussion-in%C3%A2-vitro-and-in%C3%A2-vivo-evaluation-of-novel-selective-egfr-modulator-to-inhibit-l858r-t790m-double-mutants
#10
Haoyang Zhang, Wenkui Wu, Chao Feng, Zhaogang Liu, Enhe Bai, Xueyuan Wang, Meng Lei, Hao Cheng, Huayun Feng, Jingmiao Shi, Jia Wang, Zhao Zhang, Tao Jin, Shanshan Chen, Shihe Hu, Yongqiang Zhu
Based upon the modeling binding mode of marketed AZD9291 with T790M, a series of 5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinoline derivatives were designed and synthesized with the purpose to overcome the drug resistance resulted from T790M/L858R double mutations. The most potent compound 8 showed excellent enzyme inhibitory activities and selectivity with sub nanomolar IC50 values for both the single L858R and double T790M/L858R mutant EGFRs, and was more than 8-fold selective for wild type EGFR. Compound 8 exhibited good microsomes stabilities and pharmacokinetic properties and lower binding affinity to hERG ion channel than AZD9291 and displayed strong antiproliferative activity against the H1975 non-small cell lung cancer (NSCLC) cells bearing T790M/L858R and in vivo anticancer efficacy in a human NSCLC (H1975) xenograft mouse model...
April 14, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28415575/ik-channel-activation-increases-tumor-growth-and-induces-differential-behavioral-responses-in-two-breast-epithelial-cell-lines
#11
Amy E Thurber, Michaela Nelson, Crystal L Frost, Michael Levin, William J Brackenbury, David L Kaplan
Many potassium channel families are over-expressed in cancer, but their mechanistic role in disease progression is poorly understood. Potassium channels modulate membrane potential (Vmem) and thereby influence calcium ion dynamics and other voltage-sensitive signaling mechanisms, potentially acting as transcriptional regulators. This study investigated the differential response to over-expression and activation of a cancer-associated potassium channel, the intermediate conductance calcium-activated potassium channel (IK), on aggressive behaviors in mammary epithelial and breast cancer cell lines...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28399409/direct-pharmacological-targeting-of-a-mitochondrial-ion-channel-selectively-kills-tumor-cells-in%C3%A2-vivo
#12
Luigi Leanza, Matteo Romio, Katrin Anne Becker, Michele Azzolini, Livio Trentin, Antonella Managò, Elisa Venturini, Angela Zaccagnino, Andrea Mattarei, Luca Carraretto, Andrea Urbani, Stephanie Kadow, Lucia Biasutto, Veronica Martini, Filippo Severin, Roberta Peruzzo, Valentina Trimarco, Jan-Hendrik Egberts, Charlotte Hauser, Andrea Visentin, Gianpietro Semenzato, Holger Kalthoff, Mario Zoratti, Erich Gulbins, Cristina Paradisi, Ildiko Szabo
The potassium channel Kv1.3 is highly expressed in the mitochondria of various cancerous cells. Here we show that direct inhibition of Kv1.3 using two mitochondria-targeted inhibitors alters mitochondrial function and leads to reactive oxygen species (ROS)-mediated death of even chemoresistant cells independently of p53 status. These inhibitors killed 98% of ex vivo primary chronic B-lymphocytic leukemia tumor cells while sparing healthy B cells. In orthotopic mouse models of melanoma and pancreatic ductal adenocarcinoma, the compounds reduced tumor size by more than 90% and 60%, respectively, while sparing immune and cardiac functions...
April 10, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28393180/fenofibrate-inhibits-tumour-intravasation-by-several-independent-mechanisms-in-a-3-dimensional-co-culture-model
#13
Chi Huu Nguyen, Nicole Huttary, Atanas G Atanasov, Waranya Chatuphonprasert, Stefan Brenner, Adryan Fristiohady, Junli Hong, Serena Stadler, Silvio Holzner, Daniela Milovanovic, Verena M Dirsch, Brigitte Kopp, Philipp Saiko, Liselotte Krenn, Walter Jäger, Georg Krupitza
Lymph node metastasis of breast cancer is a clinical marker of poor prognosis. Yet, there exist no therapies targeting mechanisms of intravasation into lymphatics. Herein we report on an effect of the antidyslipidemic drug fenofibrate with vasoprotective activity, which attenuates breast cancer intravasation in vitro, and describe the potential mechanisms. To measure intravasation in a 3-dimensional co-culture model MDA-MB231 and MCF-7 breast cancer spheroids were placed on immortalised lymphendothelial cell (LEC) monolayers...
April 7, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28389731/esophageal-cancer-stem-cells-are-suppressed-by-tranilast-a-trpv2-channel-inhibitor
#14
Atsushi Shiozaki, Michihiro Kudou, Daisuke Ichikawa, Hitoshi Fujiwara, Hiroki Shimizu, Takeshi Ishimoto, Tomohiro Arita, Toshiyuki Kosuga, Hirotaka Konishi, Shuhei Komatsu, Kazuma Okamoto, Yoshinori Marunaka, Eigo Otsuji
BACKGROUND: Recent evidence suggests that the targeting of membrane proteins specifically activated in cancer stem cells (CSCs) is an important strategy for cancer therapy. The objectives of the present study were to investigate the expression and activity of ion-transport-related molecules in the CSCs of esophageal squamous cell carcinoma. METHODS: Cells exhibiting strong aldehyde dehydrogenase 1 family member A1 (ALDH1A1) activity were isolated from TE8 cells by fluorescence-activated cell sorting, and CSCs were then generated with the sphere formation assay...
April 7, 2017: Journal of Gastroenterology
https://www.readbyqxmd.com/read/28379203/role-of-trpm7-in-cancer-potential-as-molecular-biomarker-and-therapeutic-target
#15
REVIEW
Nelson S Yee
The transient receptor potential melastatin-subfamily member 7 (TRPM7) is a ubiquitously expressed ion channel with intrinsic kinase activity. Molecular and electrophysiological analyses of the structure and activity of TRPM7 have revealed functional coupling of its channel and kinase activity. Studies have indicated the important roles of TRPM7 channel-kinase in fundamental cellular processes, physiological responses, and embryonic development. Accumulating evidence has shown that TRPM7 is aberrantly expressed and/or activated in human diseases including cancer...
April 5, 2017: Pharmaceuticals
https://www.readbyqxmd.com/read/28377405/the-conformational-state-of-herg1-channels-determines-integrin-association-downstream-signaling-and-cancer-progression
#16
Andrea Becchetti, Silvia Crescioli, Francesca Zanieri, Giulia Petroni, Raffaella Mercatelli, Stefano Coppola, Luca Gasparoli, Massimo D'Amico, Serena Pillozzi, Olivia Crociani, Matteo Stefanini, Antonella Fiore, Laura Carraresi, Virginia Morello, Sagar Manoli, Maria Felice Brizzi, Davide Ricci, Mauro Rinaldi, Alessio Masi, Thomas Schmidt, Franco Quercioli, Paola Defilippi, Annarosa Arcangeli
Ion channels regulate cell proliferation, differentiation, and migration in normal and neoplastic cells through cell-cell and cell-extracellular matrix (ECM) transmembrane receptors called integrins. K(+) flux through the human ether-à-go-go-related gene 1 (hERG1) channel shapes action potential firing in excitable cells such as cardiomyocytes. Its abundance is often aberrantly high in tumors, where it modulates integrin-mediated signaling. We found that hERG1 interacted with the β1 integrin subunit at the plasma membrane of human cancer cells...
April 4, 2017: Science Signaling
https://www.readbyqxmd.com/read/28373572/bidirectional-kcnq1-%C3%AE-catenin-interaction-drives-colorectal-cancer-cell-differentiation
#17
Raphael Rapetti-Mauss, Viviana Bustos, Warren Thomas, Jean McBryan, Harry Harvey, Natalia Lajczak, Stephen F Madden, Bernard Pellissier, Franck Borgese, Olivier Soriani, Brian J Harvey
The K(+) channel KCNQ1 has been proposed as a tumor suppressor in colorectal cancer (CRC). We investigated the molecular mechanisms regulating KCNQ1:β-catenin bidirectional interactions and their effects on CRC differentiation, proliferation, and invasion. Molecular and pharmacologic approaches were used to determine the influence of KCNQ1 expression on the Wnt/β-catenin signaling and epithelial-to-mesenchymal transition (EMT) in human CRC cell lines of varying stages of differentiation. The expression of KCNQ1 was lost with increasing mesenchymal phenotype in poorly differentiated CRC cell lines as a consequence of repression of the KCNQ1 promoter by β-catenin:T-cell factor (TCF)-4...
April 18, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28368405/connexin-43-channels-are-a-pathway-for-discharging-lactate-from-glycolytic-pancreatic-ductal-adenocarcinoma-cells
#18
T H Dovmark, M Saccomano, A Hulikova, F Alves, P Swietach
Glycolytic cancer cells produce large quantities of lactate that must be removed to sustain metabolism in the absence of oxidative phosphorylation. The only venting mechanism described to do this at an adequate rate is H(+)-coupled lactate efflux on monocarboxylate transporters (MCTs). Outward MCT activity is, however, thermodynamically inhibited by extracellular acidity, a hallmark of solid tumours. This inhibition would feedback unfavourably on metabolism and growth, raising the possibility that other venting mechanisms become important in under-perfused tumours...
April 3, 2017: Oncogene
https://www.readbyqxmd.com/read/28367272/eag1-k-channel-endogenous-regulation-and-functions-in-nervous-system
#19
REVIEW
Bo Han, Tursonjan Tokay, Guangming Zhang, Peng Sun, Shangwei Hou
Ether-à-go-go1 (Eag1, Kv10.1, KCNH1) K(+) channel is a member of the voltage-gated K(+) channel family mainly distributed in the central nervous system and cancer cells. Like other types of voltage-gated K(+) channels, the EAG1 channels are regulated by a variety of endogenous signals including reactive oxygen species, rendering the EAG1 to be in the redox-regulated ion channel family. The role of EAG1 channels in tumor development and its therapeutic significance have been well established. Meanwhile, the importance of hEAG1 channels in the nervous system is now increasingly appreciated...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28365825/inhibition-of-inwardly-rectifying-kir2-x-channels-by-the-novel-anti-cancer-agent-gambogic-acid-depends-on-both-pore-block-and-pip2-interference
#20
Daniel Scherer, Benedikt Schworm, Claudia Seyler, Panagiotis Xynogalos, Eberhard P Scholz, Dierk Thomas, Hugo A Katus, Edgar Zitron
The caged xanthone gambogic acid (GA) is a novel anti-cancer agent which exhibits anti-proliferative, anti-inflammatory and cytotoxic effects in many types of cancer tissues. In a recent phase IIa study, GA exhibits a favourable safety profile. However, limited data are available concerning its interaction with cardiac ion channels. Heteromeric assembly of Kir2.x channels underlies the cardiac inwardly rectifying IK1 current which is responsible for the stabilization of the diastolic resting membrane potential...
April 2, 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
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