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https://www.readbyqxmd.com/read/28766682/fasr-and-fasl-in-colorectal-cancer
#1
Magdalena Szarynska, Agata Olejniczak, Piotr Wierzbicki, Jaroslaw Kobiela, Dariusz Laski, Zbigniew Sledzinski, Krystian Adrych, Marek Guzek, Zbigniew Kmiec
Colorectal cancer (CRC) is one of the most common solid organ cancers prevalent worldwide causing, in spite of advancing therapeutic methodology, high rate of patient mortality, especially due to metastasis development. The cancer stem cell (CSC) theory of tumor growth indicates that CSCs within the tumor mass have great capacity to initiate and sustain tumor growth. Following the suggestion that Fas signaling can be engaged in apoptosis, tumor maintenance, senescence or DICE (death induced by CD95 or CD95L elimination), the attempts to broaden the knowledge concerning the relationships between CSCs features and FasR/FasL appeared to be necessary...
September 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28624961/phenotypic-and-functional-characterization-of-t-cells-in-white-matter-lesions-of-multiple-sclerosis-patients
#2
Gijsbert P van Nierop, Marvin M van Luijn, Samira S Michels, Marie-Jose Melief, Malou Janssen, Anton W Langerak, Werner J D Ouwendijk, Rogier Q Hintzen, Georges M G M Verjans
T cells are considered pivotal in the pathology of multiple sclerosis (MS), but their function and antigen specificity are unknown. To unravel the role of T cells in MS pathology, we performed a comprehensive analysis on T cells recovered from paired blood, cerebrospinal fluid (CSF), normal-appearing white matter (NAWM) and white matter lesions (WML) from 27 MS patients with advanced disease shortly after death. The differentiation status of T cells in these compartments was determined by ex vivo flow cytometry and immunohistochemistry...
June 17, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28560426/dcr3-promotes-hepatoma-cell-migration-by-downregulating-e-cadherin-expression
#3
Hongling Zhang, Xuhong Chen, Dongming Li, Lulu Cui, Xin Li, Xiufeng Ye, Xiaochun Wan
Decoy receptor 3 (DcR3), a decoy molecule belonging to the tumor necrosis factor receptor superfamily (TNFRSF), is a soluble receptor that can neutralize the biological effects of three other TNFSF members, namely, Fas ligand (FasL/TNFSF6/CD95L), LIGHT (TNFSF14) and TNF-like molecule 1A (TL1A/TNFSF15). DcR3 expression is increased in tumor cells. As such, DcR3 has been considered a potential biomarker to predict cancer invasion and progression of inflammation. However, the molecular mechanisms of DcR3 in tumor progression and metastasis remain poorly described...
May 30, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28514658/cns-macrophages-control-neurovascular-development-via-cd95l
#4
Si Chen, Nathalie Tisch, Marcel Kegel, Rosario Yerbes, Robert Hermann, Hannes Hudalla, Cecilia Zuliani, Gülce Sila Gülcüler, Klara Zwadlo, Jakob von Engelhardt, Carmen Ruiz de Almodóvar, Ana Martin-Villalba
The development of neurons and vessels shares striking anatomical and molecular features, and it is presumably orchestrated by an overlapping repertoire of extracellular signals. CNS macrophages have been implicated in various developmental functions, including the morphogenesis of neurons and vessels. However, whether CNS macrophages can coordinately influence neurovascular development and the identity of the signals involved therein is unclear. Here, we demonstrate that activity of the cell surface receptor CD95 regulates neuronal and vascular morphogenesis in the post-natal brain and retina...
May 16, 2017: Cell Reports
https://www.readbyqxmd.com/read/28445729/caspase-10-negatively-regulates-caspase-8-mediated-cell-death-switching-the-response-to-cd95l-in-favor-of-nf-%C3%AE%C2%BAb-activation-and-cell-survival
#5
Sebastian Horn, Michelle A Hughes, Ramon Schilling, Carsten Sticht, Tencho Tenev, Michaela Ploesser, Pascal Meier, Martin R Sprick, Marion MacFarlane, Martin Leverkus
Formation of the death-inducing signaling complex (DISC) initiates extrinsic apoptosis. Caspase-8 and its regulator cFLIP control death signaling by binding to death-receptor-bound FADD. By elucidating the function of the caspase-8 homolog, caspase-10, we discover that caspase-10 negatively regulates caspase-8-mediated cell death. Significantly, we reveal that caspase-10 reduces DISC association and activation of caspase-8. Furthermore, we extend our co-operative/hierarchical binding model of caspase-8/cFLIP and show that caspase-10 does not compete with caspase-8 for binding to FADD...
April 25, 2017: Cell Reports
https://www.readbyqxmd.com/read/28300842/cd95-ligand-induces-senescence-in-mismatch-repair-deficient-human-colon-cancer-via-chronic-caspase-mediated-induction-of-dna-damage
#6
Danielle A Raats, Nicola Frenkel, Susanne J van Schelven, Inne HMBorel Rinkes, Jamila Laoukili, Onno Kranenburg
CD95 is best known for its ability to induce apoptosis via a well-characterized pathway involving caspase-mediated proteolytic events. However, in apoptosis-resistant cell lines of diverse cancer types stimulation of CD95 primarily has pro-tumorigenic effects that affect many of the hallmarks of cancer. For instance, in colon cancer cells with a mutant KRAS gene CD95 primarily promotes invasion and metastasis. In the current study, we further investigated the context dependency of the consequences of CD95 activation in colon cancer...
March 16, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28273453/cd95-fas-increases-stemness-in-cancer-cells-by-inducing-a-stat1-dependent-type-i-interferon-response
#7
Abdul S Qadir, Paolo Ceppi, Sonia Brockway, Calvin Law, Liang Mu, Nikolai N Khodarev, Jung Kim, Jonathan C Zhao, William Putzbach, Andrea E Murmann, Zhuo Chen, Wenjing Chen, Xia Liu, Arthur R Salomon, Huiping Liu, Ralph R Weichselbaum, Jindan Yu, Marcus E Peter
Stimulation of CD95/Fas drives and maintains cancer stem cells (CSCs). We now report that this involves activation of signal transducer and activator of transcription 1 (STAT1) and induction of STAT1-regulated genes and that this process is inhibited by active caspases. STAT1 is enriched in CSCs in cancer cell lines, patient-derived human breast cancer, and CD95(high)-expressing glioblastoma neurospheres. CD95 stimulation of cancer cells induced secretion of type I interferons (IFNs) that bind to type I IFN receptors, resulting in activation of Janus-activated kinases, activation of STAT1, and induction of a number of STAT1-regulated genes that are part of a gene signature recently linked to therapy resistance in five primary human cancers...
March 7, 2017: Cell Reports
https://www.readbyqxmd.com/read/28223543/role-of-caspases-in-cd95-induced-biphasic-activation-of-acid-sphingomyelinase
#8
Mario Stephan, Bärbel Edelmann, Supandi Winoto-Morbach, Ottmar Janssen, Uwe Bertsch, Cristiana Perrotta, Stefan Schütze, Jürgen Fritsch
Acid sphingomyelinase (A-SMase) plays an important role in the initiation of CD95 signaling by forming ceramide-enriched membrane domains that enable clustering and activation of the death receptors. In TNF-R1 and TRAIL-R1/R2 signaling, A-SMase also contributes to the lysosomal apoptosis pathway triggered by receptor internalization. Here, we investigated the molecular mechanism of CD95-mediated A-SMase activation, demonstrating that A-SMase is located in internalized CD95-receptosomes and is activated by the CD95/CD95L complex in a biphasic manner...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28149915/myeloid-derived-suppressor-cell-arginase-1-il-17-and-cl-cd95l-an-explosive-cocktail-in-lupus
#9
COMMENT
Robin J Flynn, Patrick Legembre
No abstract text is available yet for this article.
December 2016: Annals of Translational Medicine
https://www.readbyqxmd.com/read/28078597/cd95-and-the-mrl-lpr-mouse-model
#10
Robin J Flynn
CD95 (Fas-ligand) is a key mediator of cell death in multiple setting, thus its loss within the MRL-lpr (Fas(lpr)) homozygote mice results in spontaneous autoimmunity. This is characterized by the development of arthritis and immune complex glomerulonephrosis making this strain a useful model for studying systemic lupus erythematosus. Herein we describe a method to exploit the heterozygote offspring of this strain in a model to study the effects of a CD95L blocking peptide on lupus-like disease in vivo.
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28078596/liquid-chromatography-high-resolution-mass-spectrometry-method-to-study-sphingolipid-metabolism-changes-in-response-to-cd95l
#11
Fatima Bilal, Michaël Pérès, Pauline Le Faouder, Aude Dupuy, Justine Bertrand-Michel, Nathalie Andrieu-Abadie, Thierry Levade, Bassam Badran, Ahmad Daher, Bruno Ségui
Sphingolipids are sphingoid base-containing lipids, among which some metabolites behave as bioactive molecules in various biological processes, including cell death. Whereas ceramide is now viewed as an anti-oncometabolite, leading to cancer cell death, CD95L-induced apoptosis is associated with sphingolipid changes, which likely contribute to caspase-dependent signaling pathway activation. Here, we describe Liquid Chromatography-high resolution mass spectrometry method (LC-HRMS) to analyze sphingolipid metabolism changes triggered by CD95L...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28078595/method-to-measure-sphingomyelin-synthase-activity-changes-in-response-to-cd95l
#12
Fatima Bilal, Michaël Pérès, Nathalie Andrieu-Abadie, Thierry Levade, Bassam Badran, Ahmad Daher, Bruno Ségui
Sphingomyelin synthases 1 and 2 convert the anti-oncometabolite ceramide to sphingomyelin, the most abundant sphingolipid in plasma membrane. CD95L-induced ceramide increase is associated with the caspase-dependent inhibition of sphingomyelin synthesis, which enhances the mitochondrial route to apoptosis. Knocking down sphingomyelin synthase 1 or inhibiting sphingomyelin synthesis facilitates ceramide accumulation, cytochrome c release from mitochondria, and caspase-9 activation in cancer cell upon CD95L treatment...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28078590/quantifying-cd95-cl-cd95l-implications-in-cell-mechanics-and-membrane-tension-by-atomic-force-microscopy-based-force-measurements
#13
Anaïs Sadoun, Pierre-Henri Puech
Atomic force microscopy (AFM) is an invaluable tool to investigate the structure of biological material surfaces by imaging them at nanometer scale in physiological conditions. It can also be used to measure the forces and mechanics from single molecule interaction to cell-cell adhesion. Here, we present a methodology that allows to quantify cell elastic properties (using the Young modulus) and cell membrane tension modulated by CD95/cl-CD95L interactions by coupling nanoindentation and membrane tube pulling using suitably decorated AFM levers...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28078588/boyden-chamber-assay-to-study-of-cell-migration-induced-by-metalloprotease-cleaved-cd95l
#14
Amanda Poissonnier, Patrick Legembre
CD95 receptor, also called Fas or Apo-1, is a member of the tumor necrosis factor receptors (TNF-R) superfamily (Itoh and Nagata, J Biol Chem 268:10932-10937, 1993). Its cognate ligand, CD95L, is a transmembrane cytokine, which can be cleaved by metalloproteases (Matsuno et al., J Rheumatol 28:22-28, 2001; Vargo-Gogola et al., Arch Biochem Biophys 408:155-161, 2002; Kiaei et al., Exp Neurol 205:74-81, 2007; Schulte et al., Cell Death Differ 14:1040-1049, 2007) releasing a soluble ligand into the bloodstream...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28078583/generation-and-application-of-bioluminescent-cd95-ligand-fusion-proteins
#15
Isabell Lang, Juliane Kums, Harald Wajant
The quantitative evaluation of the interaction of soluble CD95L with CD95 is not only important for a detailed understanding of CD95 biology but is also of special relevance for the characterization and development of inhibitors of this interaction. The assembly of a CD95L-CD95 complex capable to recruit intracellular factors not only involves pre-assembly of CD95 molecules in the absence of CD95L but is also modulated by cellular factors such as interaction with the actin cytoskeleton and plasma membrane compartmentation of CD95...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28078582/fluorometric-methods-for-detection-of-mitochondrial-membrane-depolarization-induced-by-cd95-activation
#16
Kenji F Shoji, Laure Debure
Mitochondria are key organelles implicated in energy supply and apoptosis. Therefore, tracking mitochondria and measuring their membrane potential is of crucial interest to monitor the CD95-mediated apoptotic signal. In this chapter, we report how we evaluate the drop of the mitochondrial transmembrane potential in leukemic cells and adherent triple negative breast cancer cells exposed to cytotoxic CD95L. We describe a simple, robust, and well-established protocol using classical fluorescent probes, DIOC6(3) and TMRM...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28078581/proximity-ligation-assay-pla-to-evaluate-disc-and-misc-composition
#17
Melissa Thomas, Patrick Legembre
Distribution of the death receptor CD95 into lipid rafts (aggregation) and/or its internalization may contribute to the implementation of the apoptotic signal at the detriment of the non-apoptotic signaling pathway [1-6]. Also CD95 can form different protein complexes via dynamic protein-protein interactions (PPIs) according to its interaction with soluble or transmembrane CD95L. Therefore, spatiotemporal identification of these PPIs is pivotal to anticipate the signaling pathway implemented in cells stimulated with different forms of CD95L...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28078578/cd95-stimulation-with-cd95l-and-disc-analysis
#18
Matthieu Le Gallo, Patrick Legembre
CD95 and its ligand CD95L play a major role in immune surveillance and homeostasis. CD95L is expressed by activated T lymphocytes and NK cells to induce apoptosis in cancer and virus-infected cells. The goal of this chapter is to describe a method used to immunoprecipitate CD95 and analyze its associated protein complex in cells stimulated with a cytotoxic CD95L (i.e., Ig-CD95L).
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28078577/production-of-the-non-apoptotic-metalloprotease-cleaved-cd95l-and-its-cytotoxic-recombinant-counterpart-designed-ig-cd95l
#19
Eléonore Lepvrier, Sophie Martin, Brigitte Collet
The ligand of CD95, CD95L (also known as FasL or CD178), is a type II transmembrane protein that belongs to the Tumor Necrosis factor (TNF) family (Fig. 1a). This membrane-bound cytokine is mainly expressed at the surface of activated T lymphocytes and natural killer cells, where it is used as an apoptotic factor to eliminate infected and transformed cells (Strasser et al., Immunity 30:180-192, 2009).
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28052242/c-flip-expression-in-foxp3-expressing-cells-is-essential-for-survival-of-regulatory-t-cells-and-prevention-of-autoimmunity
#20
Carlos Plaza-Sirvent, Marc Schuster, Yvonne Neumann, Ulrike Heise, Marina C Pils, Klaus Schulze-Osthoff, Ingo Schmitz
Regulatory T (Treg) cells are critical for the shutdown of immune responses and have emerged as valuable targets of immunotherapies. Treg cells can rapidly proliferate; however, the homeostatic processes that limit excessive Treg cell numbers are poorly understood. Here, we show that, compared to conventional T cells, Treg cells have a high apoptosis rate ex vivo correlating with low c-FLIP expression. Treg-specific deletion of c-FLIP in mice resulted in fatal autoimmune disease of a scurfy-like phenotype characterized by absent peripheral Treg cells, activation of effector cells, multi-organ immune cell infiltration, and premature death...
January 3, 2017: Cell Reports
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