Multifaceted Effects of Extracellular Adenosine Triphosphate and Adenosine in the Tumor–Host Interaction and Therapeutic Perspectives
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Cells Δγ Lineage Choice and Shapes Peripheral Purinergic P2X7
Purinergic P2X7 Receptor Drives T Cell Lineage Choice and Shapes Peripheral δγ Cells This information is current as Michela Frascoli, Jessica Marcandalli, Ursula Schenk and of October 2, 2021. Fabio Grassi J Immunol 2012; 189:174-180; Prepublished online 30 May 2012; doi: 10.4049/jimmunol.1101582 http://www.jimmunol.org/content/189/1/174 Downloaded from Supplementary http://www.jimmunol.org/content/suppl/2012/05/30/jimmunol.110158 Material 2.DC1 http://www.jimmunol.org/ References This article cites 31 articles, 15 of which you can access for free at: http://www.jimmunol.org/content/189/1/174.full#ref-list-1 Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists by guest on October 2, 2021 • Fast Publication! 4 weeks from acceptance to publication *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2012 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology Purinergic P2X7 Receptor Drives T Cell Lineage Choice and Shapes Peripheral gd Cells Michela Frascoli,* Jessica Marcandalli,* Ursula Schenk,*,1 and Fabio Grassi*,† TCR signal strength instructs ab versus gd lineage decision in immature T cells. -
Extracellular Adenosine Triphosphate and Adenosine in Cancer
Oncogene (2010) 29, 5346–5358 & 2010 Macmillan Publishers Limited All rights reserved 0950-9232/10 www.nature.com/onc REVIEW Extracellular adenosine triphosphate and adenosine in cancer J Stagg and MJ Smyth Cancer Immunology Program, Sir Donald and Lady Trescowthick Laboratories, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia Adenosine triphosphate (ATP) is actively released in the mulated the hypothesis of purinergic neurotransmission extracellular environment in response to tissue damage (Burnstock, 1972). Burnstock’s hypothesis that ATP and cellular stress. Through the activation of P2X and could be released by cells to perform intercellular P2Y receptors, extracellular ATP enhances tissue repair, signaling was initially met with skepticism, as it seemed promotes the recruitment of immune phagocytes and unlikely that a molecule that acts as an intracellular dendritic cells, and acts as a co-activator of NLR family, source of energy would also function as an extracellular pyrin domain-containing 3 (NLRP3) inflammasomes. messenger. Nevertheless, Burnstock pursued his work The conversion of extracellular ATP to adenosine, in and, together with Che Su and John Bevan, reported contrast, essentially through the enzymatic activity of the that ATP was also released from sympathetic nerves ecto-nucleotidases CD39 and CD73, acts as a negative- during stimulation (Su et al., 1971). Three decades later, feedback mechanism to prevent excessive immune responses. following the cloning and characterization of ATP and Here we review the effects of extracellular ATP and adenosine adenosine cell surface receptors, purinergic signaling is a on tumorigenesis. First, we summarize the functions of well-established concept and constitutes an expanding extracellular ATP and adenosine in the context of tumor field of research in health and disease, including cancer immunity. -
Lipid Metabolic Reprogramming: Role in Melanoma Progression and Therapeutic Perspectives
cancers Review Lipid metabolic Reprogramming: Role in Melanoma Progression and Therapeutic Perspectives 1, 1, 1 2 1 Laurence Pellerin y, Lorry Carrié y , Carine Dufau , Laurence Nieto , Bruno Ségui , 1,3 1, , 1, , Thierry Levade , Joëlle Riond * z and Nathalie Andrieu-Abadie * z 1 Centre de Recherches en Cancérologie de Toulouse, Equipe Labellisée Fondation ARC, Université Fédérale de Toulouse Midi-Pyrénées, Université Toulouse III Paul-Sabatier, Inserm 1037, 2 avenue Hubert Curien, tgrCS 53717, 31037 Toulouse CEDEX 1, France; [email protected] (L.P.); [email protected] (L.C.); [email protected] (C.D.); [email protected] (B.S.); [email protected] (T.L.) 2 Institut de Pharmacologie et de Biologie Structurale, CNRS, Université Toulouse III Paul-Sabatier, UMR 5089, 205 Route de Narbonne, 31400 Toulouse, France; [email protected] 3 Laboratoire de Biochimie Métabolique, CHU Toulouse, 31059 Toulouse, France * Correspondence: [email protected] (J.R.); [email protected] (N.A.-A.); Tel.: +33-582-7416-20 (J.R.) These authors contributed equally to this work. y These authors jointly supervised this work. z Received: 15 September 2020; Accepted: 23 October 2020; Published: 27 October 2020 Simple Summary: Melanoma is a devastating skin cancer characterized by an impressive metabolic plasticity. Melanoma cells are able to adapt to the tumor microenvironment by using a variety of fuels that contribute to tumor growth and progression. In this review, the authors summarize the contribution of the lipid metabolic network in melanoma plasticity and aggressiveness, with a particular attention to specific lipid classes such as glycerophospholipids, sphingolipids, sterols and eicosanoids. -
500 P2RX7 Agonist Treatment Boosts the Ability of IL-12-Activated CD8+ T
J Immunother Cancer: first published as 10.1136/jitc-2020-SITC2020.0500 on 10 December 2020. Downloaded from Abstracts homografts and assessed the relationship between CD5 and metastasis, and deregulation of E-cadherin is a hallmark for increased CD69 and PD-1 (markers of T cell activation and epithelial-mesenchymal transition (EMT). exhaustion) by flow cytometry. Methods The study protocol was approved by the Medical Results We report that T cell CD5 levels were higher in CD4 Ethical Committee of the Academic Medical Centre, Amster- + T cells than in CD8+ T cells in 4T1 tumour-bearing mice, dam, The Netherlands (NL42718.018.12). AIMM’s BCL6 and and that high CD5 levels on CD4+ T cells were maintained Bcl-xL immortalization method1 was used to interrogate the in peripheral organs (spleen and lymph nodes). However, both human antibody repertoire. From a carrier of a pathogenic CD4+ and CD8+ T cells recruited to tumours had reduced gene variant in the MSH6 gene diagnosed with stage IV CRC CD5 compared to CD4+ and CD8+ T cells in peripheral and liver metastasis that had been treated with avastin, capeci- organs. In addition, CD5highCD4+ T cells and CD5highCD8 tabine and oxaliplatin, peripheral-blood memory B cells were + T cells from peripheral organs exhibited higher levels of obtained 9 years after last treatment. Antibodies-containing activation and associated exhaustion compared to CD5lowCD4 supernatant of cultured B-cells were screened for binding to 3 + T cell and CD5lowCD8+ T cell from the same organs. different CRC cell lines (DLD1, LS174T and COLO205) and Interestingly, CD8+ T cells among TILs and downregulated absence of binding to fibroblast by flow cytometry. -
Non-Synonymous Single Nucleotide Polymorphisms in the P2X
Int. J. Mol. Sci. 2014, 15, 13344-13371; doi:10.3390/ijms150813344 OPEN ACCESS International Journal of Molecular Sciences ISSN 1422-0067 www.mdpi.com/journal/ijms Review Non-Synonymous Single Nucleotide Polymorphisms in the P2X Receptor Genes: Association with Diseases, Impact on Receptor Functions and Potential Use as Diagnosis Biomarkers Emily A. Caseley 1,†, Stephen P. Muench 1, Sebastien Roger 2, Hong-Ju Mao 3, Stephen A. Baldwin 1 and Lin-Hua Jiang 1,4,†,* 1 School of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK; E-Mails: [email protected] (E.A.C.); [email protected] (S.P.M.); [email protected] (S.A.B.) 2 Inserm U1069, University of Tours, Tours 37032, France; E-Mail: [email protected] 3 State Key Laboratory of Transducer Technology, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Science, Shanghai 200050, China; E-Mail: [email protected] 4 Department of Physiology and Neurobiology, Xinxiang Medical University, Xinxiang 453003, China † These authors contributed equally to this work. * Author to whom correspondence should be addressed; E-Mail: [email protected]; Tel.: +44-0-113-343-4231. Received: 6 June 2014; in revised form: 10 July 2014 / Accepted: 14 July 2014 / Published: 30 July 2014 Abstract: P2X receptors are Ca2+-permeable cationic channels in the cell membranes, where they play an important role in mediating a diversity of physiological and pathophysiological functions of extracellular ATP. Mammalian cells express seven P2X receptor genes. Single nucleotide polymorphisms (SNPs) are widespread in the P2RX genes encoding the human P2X receptors, particularly the human P2X7 receptor. -
Cell Signaling and Regulation of Metabolism Objectives
Cell Signaling and Regulation of Metabolism Objectives By the end of this lecture, students are expected to: • Differentiate different steps in signaling pathways • Describe the second messenger systems • Recognize the function of signaling pathways for • Signal transmission • Amplification • Discuss the role of signaling pathways in regulation and integration of metabolism No cell lives in isolation • Cells communicate with each other • Cells send and receive information (signals) • Information is relayed within cell to produce a response Signaling Process • Recognition of signal – Receptors • Transduction – Change of external signal into intracellular message with amplification and formation of second messenger • Effect – Modification of cell metabolism and function General Signaling Pathway Signaling Cascades Recognition • Performed by receptors • Ligand will produce response only in cells that have receptors for this particular ligand • Each cell has a specific set of receptors Different Responses to the Same Signaling Molecule. (A) Different Cells Different Responses to the Same Signaling Molecule. (B) One Cell but, Different Pathways Hypoglycemia Glucagon secretion Hepatocyte: Glucagon/receptor binding Second messenger: cAMP Response: Enzyme phosphorylation P P Glycogen synthase Glycogen phosphorylase (Inactive form) (Active form) Inhibition of glycogenesis Stimulation of glycogenolysis GTP-Dependant Regulatory Proteins (G-Proteins) G-Proteins: Trimeric membrane proteins (αβγ) G-stimulatory (Gs) and G-inhibitory (Gi) binds to GTP/GDP -
Upregulation of P2RX7 Incx3cr1-Deficient Mononuclear
The Journal of Neuroscience, May 6, 2015 • 35(18):6987–6996 • 6987 Neurobiology of Disease Upregulation of P2RX7 in Cx3cr1-Deficient Mononuclear Phagocytes Leads to Increased Interleukin-1 Secretion and Photoreceptor Neurodegeneration Shulong J. Hu,1,2,3 Bertrand Calippe,1,2,3 XSophie Lavalette,1,2,3 Christophe Roubeix,1,2,3 Fadoua Montassar,1,2,3 Michael Housset,1,2,3 Olivier Levy,1,2,3 Cecile Delarasse,4 Michel Paques,1,2,3,5 XJose´-Alain Sahel,1,2,3,5 Florian Sennlaub,1,2,3* and XXavier Guillonneau1,2,3* 1INSERM, U 968, Paris F-75012, France, 2Sorbonne Universités, UPMC Univ Paris 06, UMR S 968, Institut de la Vision, Paris, F-75012, France, 3CNRS, UMR 7210, Paris, F-75012, France, 4INSERM U 1127, CNRS UMR 7225, Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, Institut du Cerveau et de la Moelle épinière, ICM, Paris F-75013, France, and 5Centre Hospitalier National d’Ophtalmologie des Quinze-Vingts, DHU ViewMaintain, INSERM-DHOS CIC 1423, Paris, F-75012, France Photoreceptor degeneration in age-related macular degeneration (AMD) is associated with an infiltration and chronic accumulation of mononuclear phagocytes (MPs). We have previously shown that Cx3cr1-deficient mice develop age- and stress- related subretinal accumulation of MPs, which is associated with photoreceptor degeneration. Cx3cr1-deficient MPs have been shown to increase neuronal apoptosis through IL-1 in neuroinflammation of the brain. The reason for increased IL-1 secretion from Cx3cr1-deficient MPs, and whether IL-1 is responsible for increased photoreceptor apoptosis in Cx3cr1-deficient mice, has not been elucidated. -
The Regulatory Role of Key Metabolites in the Control of Cell Signaling
biomolecules Review The Regulatory Role of Key Metabolites in the Control of Cell Signaling Riccardo Milanesi, Paola Coccetti * and Farida Tripodi Department of Biotechnology and Biosciences, University of Milano-Bicocca, 20126 Milan, Italy; [email protected] (R.M.); [email protected] (F.T.) * Correspondence: [email protected]; Tel.: +39-02-6448-3521 Received: 8 May 2020; Accepted: 3 June 2020; Published: 5 June 2020 Abstract: Robust biological systems are able to adapt to internal and environmental perturbations. This is ensured by a thick crosstalk between metabolism and signal transduction pathways, through which cell cycle progression, cell metabolism and growth are coordinated. Although several reports describe the control of cell signaling on metabolism (mainly through transcriptional regulation and post-translational modifications), much fewer information is available on the role of metabolism in the regulation of signal transduction. Protein-metabolite interactions (PMIs) result in the modification of the protein activity due to a conformational change associated with the binding of a small molecule. An increasing amount of evidences highlight the role of metabolites of the central metabolism in the control of the activity of key signaling proteins in different eukaryotic systems. Here we review the known PMIs between primary metabolites and proteins, through which metabolism affects signal transduction pathways controlled by the conserved kinases Snf1/AMPK, Ras/PKA and TORC1. Interestingly, PMIs influence also the mitochondrial retrograde response (RTG) and calcium signaling, clearly demonstrating that the range of this phenomenon is not limited to signaling pathways related to metabolism. Keywords: Snf1/AMPK/SnRK1; Ras/PKA; TORC1; RTG; calcium; glucose; glycolysis; TCA; amino acids; protein-metabolite interaction 1. -
Identification of a Subset of Immunosuppressive P2RX1
ARTICLE https://doi.org/10.1038/s41467-020-20447-y OPEN Identification of a subset of immunosuppressive P2RX1-negative neutrophils in pancreatic cancer liver metastasis Xu Wang1,2,4, Li-Peng Hu1,4, Wei-Ting Qin1,4, Qin Yang1,4, De-Yu Chen2,4, Qing Li1, Kai-Xia Zhou1, Pei-Qi Huang1, Chun-Jie Xu1, Jun Li1, Lin-Li Yao1, Ya-Hui Wang1, Guang-Ang Tian1, Jian-Yu Yang3, ✉ ✉ ✉ Min-Wei Yang3, De-Jun Liu3, Yong-Wei Sun 3 , Shu-Heng Jiang 1 , Xue-Li Zhang 1 & ✉ Zhi-Gang Zhang 1 1234567890():,; The immunosuppressive microenvironment that is shaped by hepatic metastatic pancreatic ductal adenocarcinoma (PDAC) is essential for tumor cell evasion of immune destruction. Neutrophils are important components of the metastatic tumor microenvironment and exhibit heterogeneity. However, the specific phenotypes, functions and regulatory mechan- isms of neutrophils in PDAC liver metastases remain unknown. Here, we show that a subset of P2RX1-negative neutrophils accumulate in clinical and murine PDAC liver metastases. RNA sequencing of murine PDAC liver metastasis-infiltrated neutrophils show that P2RX1- deficient neutrophils express increased levels of immunosuppressive molecules, including PD-L1, and have enhanced mitochondrial metabolism. Mechanistically, the transcription factor Nrf2 is upregulated in P2RX1-deficient neutrophils and associated with PD-L1 expression and metabolic reprogramming. An anti-PD-1 neutralizing antibody is sufficient to compromise the immunosuppressive effects of P2RX1-deficient neutrophils on OVA- activated OT1 CD8+ T cells. Therefore, our study uncovers a mechanism by which metastatic PDAC tumors evade antitumor immunity by accumulating a subset of immuno- suppressive P2RX1-negative neutrophils. 1 State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, P.R. -
Plasma Membrane Receptors for Steroid Hormones in Cell Signaling and Nuclear Function
Chapter 5 / Plasma Membrane Receptors for Steroids 67 5 Plasma Membrane Receptors for Steroid Hormones in Cell Signaling and Nuclear Function Richard J. Pietras, PhD, MD and Clara M. Szego, PhD CONTENTS INTRODUCTION STEROID RECEPTOR SIGNALING MECHANISMS PLASMA MEMBRANE ORGANIZATION AND STEROID HORMONE RECEPTORS INTEGRATION OF MEMBRANE AND NUCLEAR SIGNALING IN STEROID HORMONE ACTION MEMBRANE-ASSOCIATED STEROID RECEPTORS IN HEALTH AND DISEASE CONCLUSION 1. INTRODUCTION Steroid hormones play an important role in coordi- genomic mechanism is generally slow, often requiring nating rapid, as well as sustained, responses of target hours or days before the consequences of hormone cells in complex organisms to changes in the internal exposure are evident. However, steroids also elicit and external environment. The broad physiologic rapid cell responses, often within seconds (see Fig. 1). effects of steroid hormones in the regulation of growth, The time course of these acute events parallels that development, and homeostasis have been known for evoked by peptide agonists, lending support to the con- decades. Often, these hormone actions culminate in clusion that they do not require precedent gene activa- altered gene expression, which is preceded many hours tion. Rather, many rapid effects of steroids, which have earlier by enhanced nutrient uptake, increased flux of been termed nongenomic, appear to be owing to spe- critical ions, and other preparatory changes in the syn- cific recognition of hormone at the cell membrane. thetic machinery of the cell. Because of certain homo- Although the molecular identity of binding site(s) logies of molecular structure, specific receptors for remains elusive and the signal transduction pathways steroid hormones, vitamin D, retinoids, and thyroid require fuller delineation, there is firm evidence that hormone are often considered a receptor superfamily. -
Increased Gene Copy Number of DEFA1/DEFA3 Worsens Sepsis by Inducing Endothelial Pyroptosis
Increased gene copy number of DEFA1/DEFA3 worsens sepsis by inducing endothelial pyroptosis QiXing Chena, Yang Yangb, JinChao Houb, Qiang Shua, YiXuan Yinc, WeiTao Fuc, Feng Hanc, TingJun Houc,d, CongLi Zengb, Elizabeta Nemethe, Rose Linzmeiere, Tomas Ganze,1, and XiangMing Fanga,b,1 aDepartment of Clinical Research Center, Children’s Hospital, Zhejiang University School of Medicine, 310052 Hangzhou, China; bDepartment of Anesthesiology, The First Affiliated Hospital, Zhejiang University School of Medicine, 310003 Hangzhou, China; cCollege of Pharmaceutical Sciences, Zhejiang University, 310058 Hangzhou, China; dInstitute of Functional Nano and Soft Materials, Soochow University, 215123 Suzhou, China; and eDepartment of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095 Edited by Michael Zasloff, Georgetown University Medical Center, Washington, DC, and accepted by Editorial Board Member Ruslan Medzhitov December 27, 2018 (received for review July 26, 2018) Sepsis claims an estimated 30 million episodes and 6 million deaths The mechanisms causing the quiescent endothelium to develop per year, and treatment options are rather limited. Human barrier dysfunction during sepsis might hold the key to future neutrophil peptides 1–3 (HNP1–3) are the most abundant neutro- therapeutic strategies, but they are still largely unknown. phil granule proteins but their neutrophil content varies because Defensins are short cationic, amphiphilic, cysteine-rich anti- of unusually extensive gene copy number polymorphism. A ge- microbial peptides with three or four intramolecular disulfide netic association study found that increased copy number of the bonds. They are classified as α-, β-, and θ-defensins, of which the HNP-encoding gene DEFA1/DEFA3 is a risk factor for organ dys- first two are the most common human antimicrobial peptides function during sepsis development. -
Cellular Metabolism
CST SIGNALING PATHWAY DIAGRAMS FOR Cellular Metabolism Insulin Receptor Signaling © 2003–2015 Cell Signaling Technology, Inc. Insulin Receptor SNARE TNF Glucose Complex GLUT4 p85 FlotillinCav PTEN PI3K Gab1 p110 SOCS3 Synip CAP TNFR1 Cbl PIP3 IRS Shc APS SHIP Akt2 SHP-2 PTP1B GLUT4 Crkll EHD1 GRB2 Nck Translocation TC10 C3G EHBP1 IRS-1 Crkll λ/ζ CIP4/2 PKC Fyn SOS PDK1 Rac1 mTORC2 PKCθ GRB10 Jnk GLUT4 PKCλ/ζ IKK vesicle Ras PP2A FFA 14-3-3 LKB1 NO iNOS GLUT4 AS160 Exocytosis Akt ROS c-Raf TBC1D1 AMPK PDK1 14-3-3 TSC2 PDE3B TSC1 Bad SIK2 GSK-3 PRAS40 Rheb [cAMP] MEK1/2 SGK Apoptosis SREBP CBP/p300 mTORC1 PKA Torc2 p70 Erk1/2 PP1 GS Lipin1 4E-BP1 S6K ATP-citrate Degradation ENaC lyase eIF4E HSL Glycogen Synthesis Protein Synthesis, Fatty Acid Growth, and SREBP-1 Sodium Synthesis Proliferation Lipolysis Transport Cytoplasm Erk1/2 SGK Akt2 Fatty Acid and Cholesterol Disruption of Nucleus Synthesis CBP/Torc2/CREB Complex FoxO3 FoxO4 FoxO1 Erk1/2 SREBP LXRα USF Gluconeogenesis Transcription Apoptosis, mTORC1 mTORC2 Autophagy, Lipin1 Glucose and Raptor Sin1 PRR5 GβL Lipid Metabolism Growth mTOR Rictor GβL DEPTOR mTOR DEPTOR Warburg Effect © 2010–2015 Cell Signaling Technology, Inc. Macropinocytosis and other scavenging pathways Glycolysis Growth Factors Glucose Glucose Transporters Ras Hexokinase PI3K Amino Acids NADPH NADP Ras Pentose and Lipids c-Myc Phosphate 6-P- Glucose-6-P Akt Shunt Gluconolactone 6-P- MEK1/2 NADP Ras Amino Acids Gluconate TIGAR Fructose-6-P NADPH p53 LKB1 SREBP PFK Erk1/2 Ribulose-5P AMPK Fructose mTOR Bisphosphate Nucleotide