192 results match your criteria expression cgas-sting

Priming of the cGAS-STING-TBK1 Pathway Enhances LPS-Induced Release of Type I Interferons.

Cells 2021 Apr 1;10(4). Epub 2021 Apr 1.

Department of Pediatrics, Institute for Maternal and Child Health-IRCCS Burlo Garofolo, 34137 Trieste, Italy.

Cytoplasmic nucleic acids sensing through cGAS-STING-TBK1 pathway is crucial for the production of antiviral interferons (IFNs). IFN production can also be induced by lipopolysaccharide (LPS) stimulation through Toll-like receptor 4 (TLR4) in appropriate conditions. Of note, both IFN production and dysregulated LPS-response could play a role in the pathogenesis of Systemic Lupus Erythematosus (SLE). Read More

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PBRM1 Deficiency Confers Synthetic Lethality to DNA Repair Inhibitors in Cancer.

Cancer Res 2021 Apr 22. Epub 2021 Apr 22.

ATIP-Avenir group, Inserm Unit U981, Gustave Roussy, Villejuif, France.

Inactivation of (), a specific subunit of the PBAF chromatin remodeling complex, occurs frequently in cancer, including 40% of clear cell renal cell carcinomas (ccRCC). To identify novel therapeutic approaches to targeting PBRM1-defective cancers, we used a series of orthogonal functional genomic screens that identified PARP and ATR inhibitors as being synthetic lethal with deficiency. The PBRM1/PARP inhibitor synthetic lethality was recapitulated using several clinical PARP inhibitors in a series of model systems and in a xenograft model of ccRCC. Read More

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Merkel cell polyomavirus infection induces an antiviral innate immune response in human dermal fibroblasts.

J Virol 2021 Apr 21. Epub 2021 Apr 21.

Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA

Merkel cell polyomavirus (MCPyV) infects most of the human population asymptomatically, but in rare cases leads to a highly aggressive skin cancer called Merkel cell carcinoma (MCC). MCC incidence is much higher in aging and immunocompromised populations. The epidemiology of MCC suggests that dysbiosis between the host immune response and the MCPyV infectious cycle could contribute to the development of MCPyV-associated MCC. Read More

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Hepatitis B virus nucleocapsid uncoating: biological consequences and regulation by cellular nucleases.

Emerg Microbes Infect 2021 Dec;10(1):852-864

Department of Experimental Medicine, Baruch S. Blumberg Institute, Doylestown, PA, USA.

Upon infection of hepatocyte, Hepatitis B virus (HBV) genomic DNA in nucleocapsid is transported into the nucleus and converted into a covalently closed circular (ccc) DNA to serve as the template for transcription of viral RNAs. Viral DNA in the cytoplasmic progeny nucleocapsid is another resource to fuel cccDNA amplification. Apparently, nucleocapsid disassembly, or viral genomic DNA uncoating, is an essential step for cccDNA synthesis from both infection and intracellular amplification pathways, and has a potential to activate DNA sensors and induce an innate immune response in infected hepatocytes. Read More

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December 2021

An invertebrate gene encoding a Mab21-containing protein involves in antiviral response through regulating the STING pathway.

Dev Comp Immunol 2021 Apr 16;121:104101. Epub 2021 Apr 16.

Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences, Qingdao, 266071, China; Laboratory for Marine Biology and Biotechnology, Qingdao National Laboratory for Marine Science and Technology, Qingdao, 266237, China; Center for Ocean Mega-Science, Chinese Academy of Sciences, Qingdao, 266071, China; The Innovation of Seed Design, Chinese Academy of Sciences, Wuhan, China. Electronic address:

The cGAS-STING pathway plays essential roles in detecting cytosolic dsDNA and initiating antiviral and antibacterial responses in vertebrates. However, knowledge about its function in antiviral response of invertebrates is very limited. In the present study, a gene encoding a Mab21-containing protein, a cGAS homologue, was identified from a decapod crustacean Litopenaeus vannamei and designated as LvMab21cp. Read More

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RRM2 silencing suppresses malignant phenotype and enhances radiosensitivity via activating cGAS/STING signaling pathway in lung adenocarcinoma.

Cell Biosci 2021 Apr 15;11(1):74. Epub 2021 Apr 15.

Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, Hubei, China.

Background: As one of the most common malignancy, lung adenocarcinoma (LUAD) is characterized by low 5-year survival rate. This research aimed to investigate the effects of ribonucleotide reductase regulatory subunit M2 (RRM2) on malignant biological behaviors and activation of cGAS/STING pathway. We also explored the synergistic sensitization mechanisms of RRM2 and radiotherapy. Read More

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Golgi apparatus-synthesized sulfated glycosaminoglycans mediate polymerization and activation of the cGAMP sensor STING.

Immunity 2021 Apr 7. Epub 2021 Apr 7.

Key Laboratory of Cell Proliferation and Differentiation of the Ministry of Education, School of Life Sciences, Peking University, Beijing 100871, China; Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China. Electronic address:

Activation of the cyclic guanosine monophosphate (GMP)-AMP (cGAMP) sensor STING requires its translocation from the endoplasmic reticulum to the Golgi apparatus and subsequent polymerization. Using a genome-wide CRISPR-Cas9 screen to define factors critical for STING activation in cells, we identified proteins critical for biosynthesis of sulfated glycosaminoglycans (sGAGs) in the Golgi apparatus. Binding of sGAGs promoted STING polymerization through luminal, positively charged, polar residues. Read More

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Identification and validation of the prognostic value of cyclic GMP-AMP synthase-stimulator of interferon (cGAS-STING) related genes in gastric cancer.

Bioengineered 2021 Dec;12(1):1238-1250

Department of General Surgery, People's Hospital of Jingjiang, Yangzhou University Medical Academy, Jingjiang, China.

The cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway play a significant role in the production of inflammatory cytokines and type I interferons. This study aims to develop a cGAS-STING pathway-related genes (CSRs) prediction model to predict prognosis in gastric cancer (GC). In the present study, we used The Cancer Genome Atlas (TCGA), Gene Expression Omnibus databases (GEO), CIBERSORT and Tumor Immune Estimation Resource databases (TIMER). Read More

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December 2021

cGAS-STING cytosolic DNA sensing pathway is suppressed by JAK2-STAT3 in tumor cells.

Sci Rep 2021 Mar 31;11(1):7243. Epub 2021 Mar 31.

Department of Microbiology, Immunology Programme, National University of Singapore, Singapore, 117456, Singapore.

Deficiencies in DNA repair and DNA degrading nucleases lead to accumulation of cytosolic DNA. cGAS is a critical DNA sensor for the detection of cytosolic DNA and subsequent activation of the STING signaling pathway. Here, we show that the cGAS-STING pathway was unresponsive to STING agonists and failed to induce type I interferon (IFN) expression in many tested human tumor cells including DU145 prostate cancer cells. Read More

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cGAS knockdown promotes microglial M2 polarization to alleviate neuroinflammation by inhibiting cGAS-STING signaling pathway in cerebral ischemic stroke.

Brain Res Bull 2021 Jun 18;171:183-195. Epub 2021 Mar 18.

Science and Technology Achievement Incubation Center, Kunming Medical University, Kunming, Yunnan Province, 650032, PR China. Electronic address:

Inflammation plays a pivotal role in promoting the pathophysiology of ischemic stroke (IS). Microglia is the major immunocompetent cells involved in different neuropathologies. The activation of cyclic GMP-AMP synthase (cGAS) and its downstream signaling protein-stimulator of interferon genes (STING) is increasingly recognized as a crucial determinant of neuropathophysiology. Read More

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NLRP3 protects mice from radiation-induced colon and skin damage via attenuating cGAS-STING signaling.

Toxicol Appl Pharmacol 2021 05 17;418:115495. Epub 2021 Mar 17.

Department of Gastroenterology and Hepatology, Jinling Hospital, The First School of Clinical Medicine, Southern Medical University, Nanjing 210002, China; Department of Gastroenterology and Hepatology, Jinling Hospital, Medical School of Nanjing University, 305 Zhongshan East Road, Nanjing 210002, Jiangsu Province, China. Electronic address:

In the present study, the effects of NLRP3 on radiation-induced tissue damage, including colon and skin damage in mice, and the possible mechanisms were explored in vivo and in vitro. The mice were subjected to whole abdomen radiation by timed exposure to X-ray at a cumulative dose of 14 Gy. The survival rate showed that NLRP3 deficiency increased the mortality rate in mice. Read More

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Loss of Mitochondrial Protease CLPP Activates Type I IFN Responses through the Mitochondrial DNA-cGAS-STING Signaling Axis.

J Immunol 2021 Apr 17;206(8):1890-1900. Epub 2021 Mar 17.

Department of Microbial Pathogenesis and Immunology, College of Medicine, Texas A&M University Health Science Center, Bryan, TX 77807;

Caseinolytic mitochondrial matrix peptidase proteolytic subunit (CLPP) is a serine protease that degrades damaged or misfolded mitochondrial proteins. CLPP-null mice exhibit growth retardation, deafness, and sterility, resembling human Perrault syndrome, but also display immune system alterations. However, the molecular mechanisms and signaling pathways underlying immunological changes in CLPP-null mice remain unclear. Read More

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The abscopal effect of radiation therapy.

Future Oncol 2021 May 17;17(13):1683-1694. Epub 2021 Mar 17.

Department of Medical Affairs, Gradalis, Inc, Carrollton, TX 75006, USA.

Radiation therapy (RT) in some cases results in a systemic anticancer response known as the abscopal effect. Multiple hypotheses support the role of immune activation initiated by RT-induced DNA damage. Optimal radiation dose is necessary to promote the cGAS-STING pathway in response to radiation and initiate an IFN-1 signaling cascade that promotes the maturation and migration of dendritic cells to facilitate antigen presentation and stimulation of cytotoxic T cells. Read More

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m6A methylation potentiates cytosolic dsDNA recognition in a sequence-specific manner.

Open Biol 2021 Mar 10;11(3):210030. Epub 2021 Mar 10.

Sanquin Research, University of Amsterdam, Amsterdam, The Netherlands.

Nucleic acid sensing through pattern recognition receptors is critical for immune recognition of microbial infections. Microbial DNA is frequently methylated at the N position of adenines (m6A), a modification that is rare in mammalian host DNA. We show here how that m6A methylation of 5'-GATC-3' motifs augments the immunogenicity of synthetic double-stranded (ds)DNA in murine macrophages and dendritic cells. Read More

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African Swine Fever Virus MGF-505-7R Negatively Regulates cGAS-STING-Mediated Signaling Pathway.

J Immunol 2021 Apr 12;206(8):1844-1857. Epub 2021 Mar 12.

State Key Laboratory of Veterinary Etiological Biology and World Organisation for Animal Health/National Foot and Mouth Disease Reference Laboratory, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046, Gansu, China

African swine fever virus (ASFV) is a devastating infectious disease in pigs, severely threatening the global pig industry. To efficiently infect animals, ASFV must evade or inhibit fundamental elements of the innate immune system, namely the type I IFN response. In this study, we identified that ASFV MGF-505-7R protein exerts a negative regulatory effect on STING-dependent antiviral responses. Read More

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Immune Regulation of the cGAS-STING Signaling Pathway in the Tumor Microenvironment and Its Clinical Application.

Onco Targets Ther 2021 1;14:1501-1516. Epub 2021 Mar 1.

Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.

As a DNA receptor in the cytoplasm, cyclic GMP-AMP synthase (cGAS) contributes to the recognition of abnormal DNA in the cytoplasm and contributes to the stimulator of interferon genes (STING) signaling pathway. cGAS could mediate the expression of interferon-related genes, inflammatory-related factors, and downstream chemokines, thus initiating the immune response. The STING protein is a key effector downstream of the DNA receptor pathway. Read More

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Organic dust-induced mitochondrial dysfunction could be targeted via cGAS-STING or cytoplasmic NOX-2 inhibition using microglial cells and brain slice culture models.

Cell Tissue Res 2021 Mar 9. Epub 2021 Mar 9.

Department of Biomedical Sciences, Veterinary Medicine Building, Iowa State University, Ames, IA, 50011, USA.

Organic dust (OD) exposure in animal production industries poses serious respiratory and other health risks. OD consisting of microbial products and particulate matter and OD exposure-induced respiratory inflammation are under investigation. However, the effect of OD exposure on brain remains elusive. Read More

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Signal Transducer and Activator of Transcription 3 (STAT3) Suppresses STAT1/Interferon Signaling Pathway and Inflammation in Senescent Preadipocytes.

Antioxidants (Basel) 2021 Feb 23;10(2). Epub 2021 Feb 23.

Department of Microbiology and Immunology, Weill Cornell Medicine-Qatar (WCM-Q), Qatar Foundation, Doha 24144, Qatar.

Obesity promotes premature aging and dysfunction of white adipose tissue (WAT) through the accumulation of cellular senescence. The senescent cells burden in WAT has been linked to inflammation, insulin-resistance (IR), and type 2 diabetes (T2D). There is limited knowledge about molecular mechanisms that sustain inflammation in obese states. Read More

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February 2021

Guinea pig cytomegalovirus protective T cell antigen GP83 is a functional pp65 homolog for innate immune evasion and pentamer dependent virus tropism.

J Virol 2021 Mar 3. Epub 2021 Mar 3.

Department of Microbial Pathogenesis & Immunology, Texas A&M University, Health Science Center, College of Medicine, Bryan, Texas, United States of America.

The guinea pig is the only small animal model for congenital CMV but requires species-specific guinea pig cytomegalovirus (GPCMV). Tegument protein GP83 is the presumed homolog of HCMV pp65 but gene duplication in the homolog locus in various animal CMV made it unclear if GP83 was a functional homolog. A null deletion mutant GPCMV (GP83dPC+) generated in the backdrop of glycoprotein pentamer complex (PC) positive virus, required for non-fibroblast infection, had normal growth kinetics on fibroblasts but was highly impaired on epithelial and trophoblast cells. Read More

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Chicken cGAS Senses Fowlpox Virus Infection and Regulates Macrophage Effector Functions.

Front Immunol 2020 1;11:613079. Epub 2021 Feb 1.

Department of Pathology, University of Cambridge, Cambridge, United Kingdom.

The anti-viral immune response is dependent on the ability of infected cells to sense foreign nucleic acids. In multiple species, the pattern recognition receptor (PRR) cyclic GMP-AMP synthase (cGAS) senses viral DNA as an essential component of the innate response. cGAS initiates a range of signaling outputs that are dependent on generation of the second messenger cGAMP that binds to the adaptor protein stimulator of interferon genes (STING). Read More

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February 2021

Intrinsic strategies for the evasion of cGAS-STING signaling-mediated immune surveillance in human cancer: How therapy can overcome them.

Pharmacol Res 2021 Apr 23;166:105514. Epub 2021 Feb 23.

Institute of Translational Medicine, The First Hospital of Jilin University, Changchun, China. Electronic address:

Cyclic GMP-AMP synthase (cGAS) recognizes cytosolic DNA and catalyzes the formation of cyclic GMP-AMP, which upon activation triggers the induction of stimulator of interferon genes (STING), leading to type I interferons production; these events then promote the cross-priming of dendritic cells and the initiation of a tumor-specific CD8 T cell response. However, cancer cells in the tumor microenvironment cannot trigger intrinsic cGAS-STING signaling, regardless of the expression of cGAS and STING. This dysfunctional cGAS-STING signaling enables cancer cells to evade immune surveillance, thereby promoting tumorigenesis. Read More

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Zebularine elevates STING expression and enhances cGAMP cancer immunotherapy in mice.

Mol Ther 2021 May 9;29(5):1758-1771. Epub 2021 Feb 9.

Fujian Key Laboratory of Innate Immune Biology, Biomedical Research Center of South China, College of Life Science, Fujian Normal University Qishan Campus, Fuzhou, Fujian Province 350117, China; Key Laboratory of OptoElectronic Science and Technology for Medicine of Ministry of Education, Fujian Normal University, Fuzhou, Fujian 350117, China. Electronic address:

DNA methylation abnormality is closely related to tumor occurrence and development. Chemical inhibitors targeting DNA methyltransferase (DNMTis) have been used in treating cancer. However, the impact of DNMTis on antitumor immunity has not been well elucidated. Read More

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cGAS-STING pathway expression as a prognostic tool in NSCLC.

Transl Lung Cancer Res 2021 Jan;10(1):340-354

Department of Biomedicine, Aarhus University, Aarhus, Denmark.

Background: Disease recurrence in localized lung adenocarcinoma is a major obstacle for improving the overall outcome of lung cancer. Thus, better prognostic biomarkers are needed to identify patients at risk. In order to clear cancer, immune detection of tumor cells is of vital importance. Read More

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January 2021

Human Cancer Cells Sense Cytosolic Nucleic Acids Through the RIG-I-MAVS Pathway and cGAS-STING Pathway.

Front Cell Dev Biol 2020 8;8:606001. Epub 2021 Jan 8.

Institute of Translational Medicine, The First Hospital of Jilin University, Changchun, China.

Pattern recognition receptors (PRRs) are germline-encoded host sensors of the innate immune system. Some human cancer cells have been reported to express PRRs. However, nucleic acid sensors in human cancers have not been studied in detail. Read More

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January 2021

Fever-range hyperthermia promotes cGAS-STING pathway and synergizes DMXAA-induced antiviral immunity.

Int J Hyperthermia 2021 ;38(1):30-37

Key Laboratory of System Biomedicine of the Ministry of Education, Shanghai Jiao Tong University, Shanghai, PR China.

Fever-range hyperthermia or fever-range temperature (hereafter FRT) improves survival and shortens disease duration in microbial infections. However, the mechanisms of these beneficial effects still remain elusive. We hypothesized that FRT might enhance cell responsiveness to infections by promoting cGAS-STING signaling to cause enhanced production of IFN-β. Read More

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January 2021

DNA damage-triggered activation of cGAS-STING pathway induces apoptosis in human keratinocyte HaCaT cells.

Mol Immunol 2021 03 8;131:180-190. Epub 2021 Jan 8.

Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, 110016, Liaoning, PR China; Key Laboratory of Computational Chemistry-Based Natural Antitumor Drug Research & Development, Liaoning, PR China. Electronic address:

Exposure to ultraviolet B (UVB) from sunlight causes DNA damage, serious cellular inflammation and aging, and even cell death in the skin, commonly known as sunburn, leading to cutaneous tissue disorders. DNA damage can be sensed as a danger-associated molecular pattern (DAMP) by the innate immune system. It has not been studied, however, whether cGAS-STING activation is involved in the apoptosis induced by UVB irradiation or by cisplatin treatment. Read More

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STING promotes senescence, apoptosis, and extracellular matrix degradation in osteoarthritis via the NF-κB signaling pathway.

Cell Death Dis 2021 01 4;12(1):13. Epub 2021 Jan 4.

Department of Orthopedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang Province, China.

Damaged deoxyribonucleic acid (DNA) is a primary pathologic factor for osteoarthritis (OA); however, the mechanism by which DNA damage drives OA is unclear. Previous research demonstrated that the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) participates in DNA damage response. As a result, the current study aimed at exploring the role STING, which is the major effector in the cGAS-STING signaling casacde, in OA progress in vitro, as well as in vivo. Read More

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January 2021

Metastasis and Immune Evasion from Extracellular cGAMP Hydrolysis.

Cancer Discov 2021 May 28;11(5):1212-1227. Epub 2020 Dec 28.

Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York.

Cytosolic DNA is characteristic of chromosomally unstable metastatic cancer cells, resulting in constitutive activation of the cGAS-STING innate immune pathway. How tumors co-opt inflammatory signaling while evading immune surveillance remains unknown. Here, we show that the ectonucleotidase ENPP1 promotes metastasis by selectively degrading extracellular cGAMP, an immune-stimulatory metabolite whose breakdown products include the immune suppressor adenosine. Read More

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Re-evaluation of Diadenosine Tetraphosphate (ApA) From a Stress Metabolite to Secondary Messenger.

Front Mol Biosci 2020 17;7:606807. Epub 2020 Nov 17.

Biomedical and Life Sciences, Faculty of Health and Medicine, Lancaster University, Lancaster, United Kingdom.

Cellular homeostasis requires adaption to environmental stress. In response to various environmental and genotoxic stresses, all cells produce dinucleoside polyphosphates (NpNs), the best studied of which is diadenosine tetraphosphate (ApA). Despite intensive investigation, the precise biological roles of these molecules have remained elusive. Read More

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November 2020

Mitochondrial Lon-induced mtDNA leakage contributes to PD-L1-mediated immunoescape via STING-IFN signaling and extracellular vesicles.

J Immunother Cancer 2020 12;8(2)

National Institute of Cancer Research, National Health Research Institutes, Zhunan, Miaoli, Taiwan

Background: Mitochondrial Lon is a chaperone and DNA-binding protein that functions in protein quality control and stress response pathways. The level of Lon regulates mitochondrial DNA (mtDNA) metabolism and the production of mitochondrial reactive oxygen species (ROS). However, there is little information in detail on how mitochondrial Lon regulates ROS-dependent cancer immunoescape through mtDNA metabolism in the tumor microenvironment (TME). Read More

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December 2020