keyword
https://read.qxmd.com/read/38413410/treatment-with-the-apoptosis-inhibitor-asunercept-reduces-clone-sizes-in-patients-with-lower-risk-myelodysplastic-neoplasms
#1
JOURNAL ARTICLE
Alexander Streuer, Johann-Christoph Jann, Tobias Boch, Maximilian Mossner, Vladimir Riabov, Nanni Schmitt, Eva Altrock, Qingyu Xu, Marie Demmerle, Verena Nowak, Julia Oblaender, Iris Palme, Nadine Weimer, Felicitas Rapp, Georgia Metzgeroth, Anna Hecht, Thomas Höger, Christian Merz, Wolf-Karsten Hofmann, Florian Nolte, Daniel Nowak
In low-risk Myelodysplastic Neoplasms (MDS), increased activity of apoptosis-promoting factors such as tumor necrosis factor (TNFα) and pro-apoptotic Fas ligand (CD95L) have been described as possible pathomechanisms leading to impaired erythropoiesis. Asunercept (APG101) is a novel therapeutic fusion protein blocking CD95, which has previously shown partial efficacy in reducing transfusion requirement in a clinical phase I trial for low-risk MDS patients (NCT01736436; 2012-11-26). In the current study we aimed to evaluate the effect of Asunercept therapy on the clonal bone marrow composition to identify potential biomarkers to predict response...
February 27, 2024: Annals of Hematology
https://read.qxmd.com/read/38383861/ire1-rnase-controls-cd95-mediated-cell-death
#2
JOURNAL ARTICLE
Diana Pelizzari-Raymundo, Victoria Maltret, Manon Nivet, Raphael Pineau, Alexandra Papaioannou, Xingchen Zhou, Flavie Caradec, Sophie Martin, Matthieu Le Gallo, Tony Avril, Eric Chevet, Elodie Lafont
Signalling by the Unfolded Protein Response (UPR) or by the Death Receptors (DR) are frequently activated towards pro-tumoral outputs in cancer. Herein, we demonstrate that the UPR sensor IRE1 controls the expression of the DR CD95/Fas, and its cell death-inducing ability. Both genetic and pharmacologic blunting of IRE1 activity increased CD95 expression and exacerbated CD95L-induced cell death in glioblastoma (GB) and Triple-Negative Breast Cancer (TNBC) cell lines. In accordance, CD95 mRNA was identified as a target of Regulated IRE1-Dependent Decay of RNA (RIDD)...
February 21, 2024: EMBO Reports
https://read.qxmd.com/read/38299675/membrane-bound-cd95-ligand-modulates-cd19-mediated-b-cell-receptor-signaling-and-ebv-activation
#3
JOURNAL ARTICLE
Mu Liu, Chenxu Huang, Xingchen Zhou, Congwei Jiang, Shuai Liu, Ying Gao, Linlin Kuang, Zhangmengxue Lei, Ran Jia, Jin Xu, Patrick Legembre, Xiaozhen Liang
Post-transplant lymphoproliferative disorders (PTLDs) are associated with Epstein-Barr virus (EBV) infection in transplant recipients. Most of lymphoblastoid cell lines (LCLs) derived from EBV-immortalized B cells or PTLDs are sensitive to CD95-mediated apoptosis and cytotoxic T cell (CTL) killing. CD95 ligand (CD95L) exists as a transmembrane ligand (mCD95L) or a soluble form (sCD95L). Using recombinant mCD95L and sCD95L, we observed that sCD95L does not affect LCLs. While high expression of mCD95L in CTLs promotes apoptosis of LCLs, low expression induces clathrin-dependent CD19 internalization, caspase-dependent CD19 cleavage, and proteasomal/lysosomal-dependent CD19 degradation...
February 2024: Journal of Medical Virology
https://read.qxmd.com/read/38159593/cd95-promotes-stemness-of-colorectal-cancer-cells-by-lncrna-malat1
#4
JOURNAL ARTICLE
Chenyi Gao, Kunpeng Jia, Jun Fang, Xuan Zhu, Jianming Hu, Yi Zhang, Jinxin Jiang, Xiuyan Yu, Danting Wang, Haochen Gu, Zhigang Chen
Colorectal cancer (CRC) is the second most fatal cancer. Many studies have shown that cancer stemness contributes to resistance to conventional chemotherapy and poor prognosis. However, the mechanisms involved in maintaining cancer stemness in CRC are still obscure and few clinical drugs were used to target cancer stemness. Previous studies had reported CD95 increases the stemness of cancer cells with long-term stimulation of exogenous agonist CD95 ligand (CD95L). However, the expression of CD95L is relative low in many human tumor tissues...
December 28, 2023: Life Sciences
https://read.qxmd.com/read/38047070/airway-epithelial-cells-and-macrophages-trigger-il-6-cd95-cd95l-axis-and-mediate-initial-immunopathology-of-covid-19
#5
JOURNAL ARTICLE
Thais F C Fraga-Silva, Ualter G Cipriano, Marcilio J Fumagalli, Giseli F Correa, Carlos A Fuzo, Douglas Dos-Santos, Fabiola L A C Mestriner, Christiane Becari, Andrea Teixeira-Carvalho, Jordana Coelho-Dos-Reis, Mayra G Menegueti, Luiz T M Figueiredo, Larissa Dias Cunha, Olindo A Martins-Filho, Marcelo Dias-Baruffi, Maria Auxiliadora-Martins, Rita C Tostes, Vania L D Bonato
Airway epithelial cells (AEC) infected with SARS-CoV-2 may drive the dysfunction of macrophages during COVID-19. We hypothesized that the direct interaction of AEC with macrophages mediated by CD95/CD95L or indirect interaction mediated by IL-6 signaling are key steps for the COVID-19 severe acute inflammation. The interaction of macrophages with apoptotic and infected AEC increased CD95 and CD163 expression, and induced macrophage death. Macrophages exposed to tracheal aspirate with high IL-6 levels from intubated patients with COVID-19 or to recombinant human IL-6 exhibited decreased HLA-DR expression, increased CD95 and CD163 expression and IL-1β production...
December 15, 2023: IScience
https://read.qxmd.com/read/38046264/egf-receptor-against-amphiregulin-areg-influences-costimulatory-molecules-on-monocytes-and-t-cells-and-modulates-t-cell-responses
#6
JOURNAL ARTICLE
Stephan Dreschers, Christopher Platen, Louise Oppermann, Caitlin Doughty, Andreas Ludwig, Aaron Babendreyer, Thorsten W Orlikowsky
Amphiregulin (AREG) is a ligand of the epidermal growth factor receptor (EGFR) and has been shown to regulate the phagocytosis-induced cell death of monocytes in peripheral blood. AREG-dependent apoptotic signaling engages factors of the intrinsic and extrinsic apoptotic pathway, such as BCL-2, BCL-XL, and death ligand/receptor CD95/CD95L. Here, we tested the hypothesis that AREG influences costimulatory monocyte functions, which are crucial for T-cell responses. We found a stronger expression of AREG and EGFR in monocytes compared to lymphocytes...
2023: Journal of Immunology Research
https://read.qxmd.com/read/37865305/cd95-fas-and-cd95l-fasl-mediated-non-canonical-signaling-pathways
#7
REVIEW
Layla Haymour, Mickael Jean, Cristian Smulski, Patrick Legembre
Although the interaction of CD95L (also known as FasL) with its so-called death receptor CD95 (Fas) induces an apoptotic signal responsible for the elimination of infected and cancer cells and maintenance of tissue homeostasis, this receptor can also implement non apoptotic signaling pathways. This latter signaling is involved in metastatic dissemination in certain cancers and the severity of auto-immune disorders. The signaling complexity of this pair is increased by the fact that CD95 expression itself seems to contribute to oncogenesis via a CD95L-independent manner and, that both ligand and receptor might interact with other partners modulating their pathophysiological functions...
October 19, 2023: Biochimica et Biophysica Acta. Reviews on Cancer
https://read.qxmd.com/read/37837385/cd95l-concatemers-highlight-different-stoichiometries-of-cd95-mediated-apoptotic-and-non-apoptotic-pathways
#8
JOURNAL ARTICLE
Eden Lebrault, Christelle Oblet, Keerthi Kurma, Nicolas Levoin, Robin Jeannet, Mickael Jean, Pierre Vacher, Patrick Legembre
To better understand the stoichiometry of CD95L required to trigger apoptotic and non-apoptotic signals, we generated several CD95L concatemers from dimer to hexamer conjugated via a flexible link (GGGGS)2 . These ligands reveal that although the hexameric structure is the best stoichiometry to trigger cell death, a dimer is sufficient to induce the apoptotic response in CD95-sensitive Jurkat cells. Interestingly, only trimeric and hexameric forms can implement a potent Ca2+ response, suggesting that while CD95 aggregation controls the implementation of the apoptotic signal, both aggregation and conformation are required to implement the Ca2+ pathway...
October 14, 2023: European Journal of Immunology
https://read.qxmd.com/read/37353767/unsolved-mystery-of-fas-mononuclear-cells-may-have-trouble-dying-in-patients-with-sj%C3%A3-gren-s-syndrome
#9
JOURNAL ARTICLE
Irena Lindrova, Martina Kolackova, Tereza Svadlakova, Radka Vankova, Marcela Chmelarova, Michaela Rosecka, Eva Jozifkova, Martin Sembera, Jan Krejsek, Radovan Slezak
BACKGROUND: Patients with Sjögren's syndrome, like other patients with autoimmune disorders, display dysregulation in the function of their immune system. Fas and Fas Ligand (FasL) are among the dysregulated proteins. METHODS: We studied Fas and FasL on IL-2Rα+ cells and in serum of patients with Sjögren's syndrome (n = 16) and healthy individuals (n = 16); both from same ethnic and geographical background. We used flow cytometry and enzyme-linked immunosorbent for this purpose...
June 23, 2023: BMC Immunology
https://read.qxmd.com/read/37191832/the-abscopal-effect-of-anti-cd95-and-radiotherapy-in-melanoma
#10
JOURNAL ARTICLE
Jixiang Xu, JiangFeng He, JiaJun He, Yuanmin He, DaoJun Zhang, Rui Kong, Kena Dan
BACKGROUND: Radiotherapy (RT) is frequently adopted to control cancer cell proliferation, which is achieved by altering the tumor microenvironment (TME) and immunogenicity. Apoptosis of cancer cells is the major effect of radiation on tumor tissues. Fas/APO-1(CD95) receptors on the cell membrane are death receptors that can be activated by diverse factors, including radiation and integration with CD95L on CD8+ T cells. The abscopal effect is defined as tumor regression out of the local RT field, and it is produced through anti-tumor immunity...
May 16, 2023: Discover. Oncology
https://read.qxmd.com/read/37085701/a-mathematical-modeling-technique-to-understand-the-role-of-decoy-receptors-in-ligand-receptor-interaction
#11
JOURNAL ARTICLE
Subrata Dey, Aditi Ghosh, Malay Banerjee
The ligand-receptor interaction is fundamental to many cellular processes in eukaryotic cells such as cell migration, proliferation, adhesion, signaling and so on. Cell migration is a central process in the development of organisms. Receptor induced chemo-tactic sensitivity plays an important role in cell migration. However, recently some receptors identified as decoy receptors, obstruct some mechanisms of certain regular receptors. DcR3 is one such important decoy receptor, generally found in glioma cell, RCC cell and many various malignant cells which obstruct some mechanism including apoptosis cell-signaling, cell inflammation, cell migration...
April 21, 2023: Scientific Reports
https://read.qxmd.com/read/37059938/cd95-fas-ligand-mrna-is-toxic-to-cells-through-more-than-one-mechanism
#12
JOURNAL ARTICLE
Ashley Haluck-Kangas, Madelaine Fink, Elizabeth T Bartom, Marcus E Peter
CD95/Fas ligand (CD95L) induces apoptosis through protein binding to the CD95 receptor. However, CD95L mRNA also induces toxicity in the absence of CD95 through induction of DISE (Death Induced by Survival Gene Elimination), a form of cell death mediated by RNA interference (RNAi). We now report that CD95L mRNA processing generates a short (s)RNA nearly identical to shL3, a commercial CD95L-targeting shRNA that led to the discovery of DISE. Neither of the miRNA biogenesis proteins Drosha nor Dicer are required for this processing...
April 15, 2023: Mol Biomed
https://read.qxmd.com/read/36902036/tumor-necrosis-factor-family-members-and-myocardial-ischemia-reperfusion-injury-state-of-the-art-and-therapeutic-implications
#13
REVIEW
Antonella Galeone, Maria Grano, Giacomina Brunetti
Ischemic heart disease is the principal cause of death worldwide and clinically manifests as myocardial infarction (MI), stable angina, and ischemic cardiomyopathy. Myocardial infarction is defined as an irreversible injury due to severe and prolonged myocardial ischemia inducing myocardial cell death. Revascularization is helpful in reducing loss of contractile myocardium and improving clinical outcome. Reperfusion rescues myocardium from cell death but also induces an additional injury called ischemia-reperfusion injury...
February 27, 2023: International Journal of Molecular Sciences
https://read.qxmd.com/read/36821824/correction-the-naturally-processed-cd95l-elicits-a-c-yes-calcium-pi3k-driven-cell-migration-pathway
#14
Sébastien Tauzin, Benjamin Chaigne-Delalande, Eric Selva, Nadine Khadra, Sophie Daburon, Cécile Contin-Bordes, Patrick Blanco, Jacques Le Seyec, Thomas Ducret, Laurent Counillon, Jean-François Moreau, Paul Hofman, Pierre Vacher, Patrick Legembre
[This corrects the article DOI: 10.1371/journal.pbio.1001090.].
February 2023: PLoS Biology
https://read.qxmd.com/read/36694998/metalloprotease-mediated-cleavage-of-cd95-ligand
#15
JOURNAL ARTICLE
Vesna Risso, Mélissa Thomas, Blandine Guével, Regis Lavigne, Emmanuelle Com, Sophie Martin, Manon Nivet, Charles Pineau, Luc Negroni, Élodie Lafont, Éric Chevet, Leif A Eriksson, Matthieu Le Gallo
CD95 is a member of the TNF receptor superfamily that is ubiquitously expressed in healthy and pathological tissues. Stimulation of CD95 by its physiological ligand CD95L induces its oligomerization leading in turn to the transduction of either apoptotic or non-apoptotic signals. CD95L can exist as both membrane-anchored and soluble forms (sCD95L), the latter resulting from the proteolytic cleavage of the former. Candidate proteases able to achieve CD95L cleavage were identified as matrix metalloproteases (MMP) due to their demonstrated ability to cleave other TNF superfamily ligands...
January 24, 2023: FEBS Journal
https://read.qxmd.com/read/36629505/cd95-fas-ligand-induced-toxicity
#16
JOURNAL ARTICLE
Ashley Haluck-Kangas, Marcus E Peter
The role of CD95/Fas ligand (CD95L/FasL) in the induction of CD95-mediated extrinsic apoptosis is well characterized. Trimerized, membrane-bound CD95L ligates the CD95 receptor activating downstream signaling resulting in the execution of cells by caspase proteins. However, the expression of CD95L has been reported to induce cell death in contexts in which this pathway is unlikely to be activated, such as in cell autonomous activation induced cell death (AICD) and in CD95-resistant cancer cell lines. Recent data suggests that the CD95L mRNA exerts toxicity through death induced by survival gene elimination (DISE)...
January 11, 2023: Biochemical Society Transactions
https://read.qxmd.com/read/36544756/role-of-metalloproteases-in-the-cd95-signaling-pathways
#17
REVIEW
Laurent Devel, Nicolas Guedeney, Sarah Bregant, Animesh Chowdhury, Mickael Jean, Patrick Legembre
CD95L (also known as FasL or CD178) is a member of the tumor necrosis family (TNF) superfamily. Although this transmembrane ligand has been mainly considered as a potent apoptotic inducer in CD95 (Fas)-expressing cells, more recent studies pointed out its role in the implementation of non-apoptotic signals. Accordingly, this ligand has been associated with the aggravation of inflammation in different auto-immune disorders and in the metastatic occurrence in different cancers. Although it remains to decipher all key factors involved in the ambivalent role of this ligand, accumulating clues suggest that while the membrane bound CD95L triggers apoptosis, its soluble counterpart generated by metalloprotease-driven cleavage is responsible for its non-apoptotic functions...
2022: Frontiers in Immunology
https://read.qxmd.com/read/36516955/trotnfsf6-a-tumor-necrosis-factor-ligand-superfamily-member-promotes-antibacterial-immune-response-of-golden-pompano-trachinotus-ovatus
#18
JOURNAL ARTICLE
Chunsheng Liu, Lu Wang, Xiaojuan Chen, Zhiru Liu, Yang Shen, Ying Wu, Yongcan Zhou, Jianlong Li, Zhenjie Cao, Yun Sun
Tumor necrosis factor ligand superfamily member 6 (TNFSF6), also known as FasL/CD95L, is essential for maintaining the body's immune homeostasis. However, the current reports on TNFSF6 in fish are relatively scarce. In the present study, we conducted functional analyses of a TNFSF6 (TroTNFSF6) from the teleost fish golden pompano (Trachinotus ovatus). TroTNFSF6 is composed of 228 amino acids and has a low similarity with other species (9.65%-58.79%). TroTNFSF6 was expressed in the 11 tissues tested and was significantly up-regulated after Edwardsiella tarda infection...
December 11, 2022: Fish & Shellfish Immunology
https://read.qxmd.com/read/36505426/the-dual-role-of-the-cd95-and-cd95l-signaling-pathway-in-glioblastoma
#19
REVIEW
Yanrui Zhang, Taian Jin, Zhangqi Dou, Boxing Wei, Buyi Zhang, Chongran Sun
Binding of CD95, a cell surface death receptor, to its homologous ligand CD95L, transduces a cascade of downstream signals leading to apoptosis crucial for immune homeostasis and immune surveillance. Although CD95 and CD95L binding classically induces programmed cell death, most tumor cells show resistance to CD95L-induced apoptosis. In some cancers, such as glioblastoma, CD95-CD95L binding can exhibit paradoxical functions that promote tumor growth by inducing inflammation, regulating immune cell homeostasis, and/or promoting cell survival, proliferation, migration, and maintenance of the stemness of cancer cells...
2022: Frontiers in Immunology
https://read.qxmd.com/read/36355258/crispr-cas9-mediated-abrogation-of-cd95l-cd95-signaling-induced-glioma-cell-growth-and-immunosuppression-increases-survival-in-murine-glioma-models
#20
JOURNAL ARTICLE
Clara Quijano-Rubio, Manuela Silginer, Michael Weller
PURPOSE: Glioblastoma is the most common brain tumor in adults and is virtually incurable. Therefore, new therapeutic strategies are urgently needed. Over the last decade, multiple growth-promoting functions have been attributed to CD95, a prototypic death receptor well characterized as an apoptosis mediator upon CD95L engagement. Strategic targeting of non-apoptotic or apoptotic CD95 signaling may hold anti-glioblastoma potential. Due to its antithetic nature, understanding the constitutive role of CD95 signaling in glioblastoma is indispensable...
November 10, 2022: Journal of Neuro-oncology
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