Cytoplasmic chromatin triggers inflammation in senescence and cancer
Open accessAbstract
Chromatin is traditionally viewed as a nuclear entity that regulates gene expression and silencing. However, we recently discovered the presence of cytoplasmic chromatin fragments that pinch off from intact nuclei of primary cells during senescence, a form of terminal cell-cycle arrest associated with pro-inflammatory responses. The functional significance of chromatin in the cytoplasm is unclear. Here we show that cytoplasmic chromatin activates the innate immunity cytosolic DNA-sensing cGAS-STING (cyclic GMP-AMP synthase linked to stimulator of interferon genes) pathway, leading both to short-term inflammation to restrain activated oncogenes and to chronic inflammation that associates with tissue destruction and cancer. The cytoplasmic chromatin-cGAS-STING pathway promotes the senescence-associated secretory phenotype in primary human cells and in mice. Mice deficient in STING show impaired immuno-surveillance of oncogenic RAS and reduced tissue inflammation upon ionizing radiation. Furthermore, this pathway is activated in cancer cells, and correlates with pro-inflammatory gene expression in human cancers. Overall, our findings indicate that genomic DNA serves as a reservoir to initiate a pro-inflammatory pathway in the cytoplasm in senescence and cancer. Targeting the cytoplasmic chromatin-mediated pathway may hold promise in treating inflammation-related disorders.
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cGAS and STING are major regulators of the SASP programme across species, probably by activating NF-κB and IRF3.
“The DNA sensor cGAS and the adaptor protein STING have been reported to be major regulators of the SASP programme across species, presumably by activating NF-κB and the interferon response factor IRF3 (REFS60,112,113).”
From Cellular senescence in ageing: from mechanisms to therapeutic opportunities (2021) · cites this paper as [60]
The supplied Abstract passages (no page specified) report that cGAS–STING is required for the SASP in human cells, that STING mediates a SASP response in mice, and that the pathway activates NF-κB. They distinguish IRF3 as part of the interferon pathway and report that interferon genes are not induced in senescence; they do not support IRF3 activation as a mechanism of the SASP. (LLM, conf=0.88)
Experimental — accuracy not yet measuredCellular senescence is accompanied by substantial reorganization of the nuclear envelope and a breakdown in nucleocytoplasmic trafficking, including altered expression and degradation of Lamin B1, and formation of cytoplasmic chromatin fragments.
“Cellular senescence is accompanied by substantial reorganization of the nuclear envelope and a breakdown in nucleocytoplasmic trafficking, including altered expression and degradation of Lamin B1, and the formation of cytoplasmic chromatin fragments (CCFs) [38–45].”
From Chemically induced reprogramming to reverse cellular aging (2023) · cites this paper as [39]
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredThe cGAS-STING pathway regulates cellular senescence.
“We and others have previously described a role of the cGAS–STING pathway in the regulation of cellular senescence—a hallmark of ageing5–8.”
From cGAS–STING drives ageing-related inflammation and neurodegeneration (2023) · cites this paper as [7]
The passage labeled Abstract (page unavailable) shows that cGAS–STING regulates the senescence-associated secretory phenotype (SASP), a key feature of senescence. It also reports that disrupting the pathway does not affect several senescence markers or reverse established senescence, so the broader claim that it regulates cellular senescence needs that qualification. (LLM, conf=0.86)
Experimental — accuracy not yet measuredLoss of nuclear lamina can release cytosolic chromatin fragments into the cytoplasm of senescent cells.
“Loss of nuclear lamina can lead to the release of cytosolic chromatin fragments (CCFs) in the cytoplasm of senescent cells58–60”
From Cellular senescence in ageing: from mechanisms to therapeutic opportunities (2021) · cites this paper as [60]
Downregulation of Lamin B1 leads to collapse of the nuclear envelope, which can trigger release of chromatin fragments from the nucleus to the cytosol, termed cytoplasmic chromatin fragments.
“Downregulation of Lamin B1 leads to collapse of the nuclear envelope, which can trigger release of chromatin fragments from the nucleus to the cytosol, termed cytoplasmic chromatin fragments (CCF).68”
From Cellular senescence and senescence-associated secretory phenotype via the cGAS-STING signaling pathway in cancer (2020) · cites this paper as [68]
Inhibiting the cGAS-STING signaling pathway impaired the immuno-surveillance of senescent hepatocytes and premalignant hepatocytes, resulting in tumorigenesis in the liver.
“However, Dou et al68 demonstrated that inhibiting the cGAS‐STING signaling pathway impaired the immuno‐surveillance of senescent hepatocytes and premalignant hepatocytes, resulting in tumorigenesis in the liver.”
From Cellular senescence and senescence-associated secretory phenotype via the cGAS-STING signaling pathway in cancer (2020) · cites this paper as [68]
The cGAS/STING pathway is considered a key regulator of SASP induction.
“The cGAS/STING pathway is considered a key regulator of SASP induction (Dou et al. 2017; Glück et al. 2017; Yang et al. 2017).”
From Senescence and the SASP: many therapeutic avenues (2020) · cites this paper as Dou et al. 2017
DNA damage products and retroelement amplification are upstream triggers of cGAS in senescence.
“Previous research has revealed DNA damage products5–7 and retroelement amplification52 as upstream triggers of cGAS in senescence.”
From cGAS–STING drives ageing-related inflammation and neurodegeneration (2023) · cites this paper as [7]
Telomeric DNA damage is more senescence-specific and can be quantified by combining FISH for telomeric sequences with immunostaining for DNA damage response proteins.
“Telomeric DNA damage is more senescence-specific and can be quantified by combining fluorescence in situ hybridization (FISH) for telomeric sequences and immunostaining (immunoFISH) for DSB-associated proteins22.”
From Guidelines for minimal information on cellular senescence experimentation in vivo (2024) · cites this paper as [22]
The Methods section on immunofluorescence and quantification describes staining and counting DNA-damage markers, but not telomeric FISH or immunoFISH. Searches for telomeric DNA damage and telomere-associated damage foci found no passage in our copy establishing that the measure is more senescence-specific or describing the claimed combined assay. Page numbers were not available. (LLM, conf=0.76)
Experimental — accuracy not yet measuredMechanisms implicated in accumulation of cytoplasmic DNA in senescent cells include compromised nuclear integrity due to loss of Lamin B1 and downregulation of cytoplasmic DNAases such as DNAase 2 and TREX1.
“The mechanisms implicated in the accumulation of cytoplasmic DNA in senescent cells include compromised nuclear integrity due to loss of the nuclear lamina protein, Lamin B1 (Dou et al., 2017) and downregulation of cytoplasmic DNAases such as DNAase 2 and TREX1 (Takahashi et al., 2018) frequently observed in senescent cells.”
From Mechanisms of Cellular Senescence: Cell Cycle Arrest and Senescence Associated Secretory Phenotype (2021) · cites this paper as Dou et al., 2017
Cytoplasmic chromatin fragments and transposable elements can stimulate cGAS-STING pathway and regulate SASP both in vitro and in vivo where senescence was induced by different stimuli.
“Recent studies have revealed that cytoplasmic chromatin fragments and transposable elements can stimulate cyclic GMP–AMP synthase linked to stimulator of interferon genes (cGAS-STING) pathway and regulate SASP both in vitro and in vivo where senescence was induced by different stimuli (Dou et al., 2017; Glück et al., 2017; Yang et al., 2017; Li and Chen, 2018).”
From Mechanisms of Cellular Senescence: Cell Cycle Arrest and Senescence Associated Secretory Phenotype (2021) · cites this paper as Dou et al., 2017
Loss of cGAS compromised senescence due to reduced SASP in different in vivo models and accelerated spontaneous immortalisation of MEFs, highlighting crucial role of cGAS/STING pathway in tumor suppression due to immune-mediated clearance of premalignant cells.
“Loss of cGAS compromised senescence due to reduced SASP in different in vivo models and also accelerated the spontaneous immortalisation of mouse embryonic fibroblasts thereby highlighting the crucial role of the cGAS/STING pathway in tumor suppression due to immune-mediated clearance of premalignant cells (Dou et al., 2017; Glück et al., 2017; Umbreit and Pellman, 2017; Yang et al., 2017).”
From Mechanisms of Cellular Senescence: Cell Cycle Arrest and Senescence Associated Secretory Phenotype (2021) · cites this paper as Dou et al., 2017
Senescence-associated DNA damage is sensed through the cGAS-STING pathway, which activates IRF3 and NF-κB and induces interferon and SASP responses.
“Senescence-associated DNA damage is sensed via the cGAS–STING pathway, which activates the transcription factors interferon regulatory factor 3 (IRF3) and NF-κB, thereby inducing an interferon and SASP response55–58”
From COVID-19 and cellular senescence (2023) · cites this paper as [55]
Once CCF enter the cytoplasm, they are sensed by the cGAS-STING pathway.
“Once CCF enter the cytoplasm, they are sensed by the cGAS-STING pathway (Dou et al., 2017; Gluck et al., 2017; Takahashi et al., 2018; Yang et al., 2017) (Fig. 2).”
From Cytoplasmic DNA: sources, sensing, and role in aging and disease (2021) · cites this paper as Dou et al., 2017
cGAS-STING activation in senescent cells leads to NF-κB activation of SASP genes rather than an interferon gene program, potentially because p38-MAPK represses interferon genes.
“cGAS-STING activation leads to NF-κB activation of SASP genes downstream of STING instead of an interferon gene program, potentially due to p38-MAPK repression of interferon genes in senescent cells (Dou et al., 2017).”
From Cytoplasmic DNA: sources, sensing, and role in aging and disease (2021) · cites this paper as Dou et al., 2017
This cytokine phenotype in senescent cells is proposed to require p38-MAPK activity in part.
“a phenotype which is thought to be partly dependent on p38-MAPK activation in senescent cells (Dou et al., 2017)”
From Cytoplasmic DNA: sources, sensing, and role in aging and disease (2021) · cites this paper as Dou et al., 2017
In cancer cells, cGAS activation by micronuclei is well established as inducing interferon genes.
“although MN-dependent cGAS activation of interferon genes is well documented in cancer cells”
From Cytoplasmic DNA: sources, sensing, and role in aging and disease (2021) · cites this paper as Dou et al., 2017
When CCF activate cGAS in senescent cells, the response usually involves NF-κB-dependent cytokines.
“CCF activation of cGAS in senescent cells is typically associated with an NF-κB-dependent cytokine response”
From Cytoplasmic DNA: sources, sensing, and role in aging and disease (2021) · cites this paper as Dou et al., 2017
cGAS catalyzes production of the second messenger cGMP that binds STING, resulting in phosphorylation of IRF3 and NF-κB and stimulating production of type I interferons and inflammatory cytokines.
“cGAS catalyzes the production of the second messenger cGMP that binds to stimulator of interferon genes (STING). This results in the phosphorylation of both interferon-regulatory factor 3 (IRF3) and of NF-κB transcription factors, thereby stimulating respectively the production of type I interferons and inflammatory cytokines [171,172,173,174].”
From Mechanisms and Regulation of Cellular Senescence (2021) · cites this paper as [171]
The nuclear envelope of micronuclei is unstable and can rupture, leading to exposure of micronuclear DNA that induces a cellular immune response via cGAS.
“The nuclear envelope of these micronuclei is unstable and can rupture, leading to the exposure of micronuclear DNA that induces a cellular immune response via cGAS [171,172,173].”
From Mechanisms and Regulation of Cellular Senescence (2021) · cites this paper as [171]
Loss of cGAS and/or STING function reduces SASP factor levels in primary human cells and in mouse models of DNA damage-induced senescence.
“Consistently, loss of cGAS and/or STING function reduces SASP factor levels in primary human cells and in mouse models of DNA damage-induced senescence [171,172,173].”
From Mechanisms and Regulation of Cellular Senescence (2021) · cites this paper as [171]
CCFs formation relies on constitutive interaction between lamin B1 and LC3.
“Therefore, CCFs formation relies on the constitutive interaction between lamin B1 and LC3, and CCFs formation is required to reinforce OIS by initiating the SASP program [171,172].”
From Mechanisms and Regulation of Cellular Senescence (2021) · cites this paper as [171]
CCFs formation is required to reinforce OIS by initiating the SASP program.
“Therefore, CCFs formation relies on the constitutive interaction between lamin B1 and LC3, and CCFs formation is required to reinforce OIS by initiating the SASP program [171,172].”
From Mechanisms and Regulation of Cellular Senescence (2021) · cites this paper as [171]
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Cites
The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity
Barretina, J., Caponigro, G., Stransky, N., Venkatesan, K., Margolin, A. A., Kim, S., Wilson, C. J., Lehár, J., Kryukov, G. V., Sonkin, D., et al. (2012) · Nature · doi:10.1038/nature11003 · Cited by 7,950 · see citing works
Cyclic GMP-AMP Synthase Is a Cytosolic DNA Sensor That Activates the Type I Interferon Pathway
Sun, L., Wu, J., Du, F., Chen, X., & Chen, Z. J. (2013) · Science · doi:10.1126/science.1232458 · Cited by 4,996 · see citing works
STING is an endoplasmic reticulum adaptor that facilitates innate immune signalling
Ishikawa, H., & Barber, G. N. (2008) · Nature · doi:10.1038/nature07317 · Cited by 3,576 · see citing works
Self-citationAging, Cellular Senescence, and Cancer
Campisi, J. (2013) · Annual Review of Physiology · doi:10.1146/annurev-physiol-030212-183653 · Cited by 2,954 · cited 1× · see citing works
“, Campisi, J. & Toussaint, O. Protocols to detect senescence-associated beta-galactosidase (SA-betagal) activity, a biomarker of senescent cells in culture and in vivo. Nat Protoc 4, 1798-1806, doi:10.1038/nprot.2009.191 nprot.2009.191 [pii] (2009). 32 Abe, T. et al. STING recognition of cytoplasmic DNA instigates cel…”
BackgroundInfluentialThe complex language of chromatin regulation during transcription
Berger, S. L. (2007) · Nature · doi:10.1038/nature05915 · Cited by 2,768 · see citing works
Self-citationSTING regulates intracellular DNA-mediated, type I interferon-dependent innate immunity
Ishikawa, H., Ma, Z., & Barber, G. N. (2009) · Nature · doi:10.1038/nature08476 · Cited by 2,759 · see citing works
Self-citationCyclic GMP-AMP Is an Endogenous Second Messenger in Innate Immune Signaling by Cytosolic DNA
Wu, J., Sun, L., Chen, X., Du, F., Shi, H., Chen, C., & Chen, Z. J. (2012) · Science · doi:10.1126/science.1229963 · Cited by 2,574 · see citing works
A complex secretory program orchestrated by the inflammasome controls paracrine senescence
Acosta, J. C., Banito, A., Wuestefeld, T., Georgilis, A., Janich, P., Morton, J. P., Athineos, D., Kang, T.-W., Lasitschka, F., Andrulis, M., et al. (2013) · Nature Cell Biology · doi:10.1038/ncb2784 · Cited by 2,278 · see citing works
Persistent DNA damage signalling triggers senescence-associated inflammatory cytokine secretion
Rodier, F., Coppé, J.-P., Patil, C. K., Hoeijmakers, W. A. M., Muñoz, D. P., Raza, S. R., Freund, A., Campeau, E., Davalos, A. R., & Campisi, J. (2009) · Nature Cell Biology · doi:10.1038/ncb1909 · Cited by 2,232 · see citing works
Debacq-Chainiaux, F., Erusalimsky, J. D., Campisi, J., & Toussaint, O. (2009) · Nature Protocols · doi:10.1038/nprot.2009.191 · Cited by 1,668 · see citing works
Senescence surveillance of pre-malignant hepatocytes limits liver cancer development
Kang, T.-W., Yevsa, T., Woller, N., Hoenicke, L., Wuestefeld, T., Dauch, D., Hohmeyer, A., Gereke, M., Rudalska, R., Potapova, A., et al. (2011) · Nature · doi:10.1038/nature10599 · Cited by 1,621 · see citing works
Inflammatory networks during cellular senescence: causes and consequences.
Freund, A., Orjalo, A. V., Desprez, P.-Y., & Campisi, J. (2010) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2010.03.003 · Cited by 1,354 · see citing works
STING: infection, inflammation and cancer.
Barber, G. N. (2015) · Nature Reviews Immunology · doi:10.1038/nri3921 · Cited by 1,313 · see citing works
Self-citationTumor Interferon Signaling Regulates a Multigenic Resistance Program to Immune Checkpoint Blockade
Benci, J. L., Xu, B., Qiu, Y., Wu, T. J., Dada, H., Twyman-Saint Victor, C., Cucolo, L., Lee, D. S. M., Pauken, K. E., Huang, A. C., et al. (2016) · Cell · doi:10.1016/j.cell.2016.11.022 · Cited by 1,216 · see citing works
Innate immune sensing of cytosolic chromatin fragments through cGAS promotes senescence
Glück, S., Guey, B., Gulen, M. F., Wolter, K., Kang, T.-W., Schmacke, N. A., Bridgeman, A., Rehwinkel, J., Zender, L., & Ablasser, A. (2017) · Nature Cell Biology · doi:10.1038/ncb3586 · Cited by 1,196 · see citing works
Chromothripsis from DNA damage in micronuclei
Zhang, C., Spektor, A., Cornils, H., Francis, J. M., Jackson, E. K., Liu, S., Meyerson, M. M., & Pellman, D. S. (2015) · Nature · doi:10.1038/nature14493 · Cited by 1,153 · see citing works
Chien, Y., Scuoppo, C., Wang, X., Fang, X., Balgley, B., Bolden, J. E., Premsrirut, P., Luo, W., Chicas, A., Lee, C. S., et al. (2011) · Genes & Development · doi:10.1101/gad.17276711 · Cited by 1,046 · see citing works
Lamin B1 loss is a senescence-associated biomarker
Freund, A., Laberge, R.-M., Demaria, M., & Campisi, J. (2012) · Molecular Biology of the Cell · doi:10.1091/mbc.e11-10-0884 · Cited by 1,046 · see citing works
Freund, A., Patil, C. K., & Campisi, J. (2011) · The EMBO Journal · doi:10.1038/emboj.2011.69 · Cited by 1,039 · see citing works
cGAS is essential for cellular senescence
Yang, H., Wang, H., Ren, J., Chen, Q., & Chen, Z. J. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1705499114 · Cited by 1,009 · see citing works
Carcinoma–astrocyte gap junctions promote brain metastasis by cGAMP transfer
Chen, Q., Boire, A., Jin, X., Valiente, M., Er, E. E., Lopez-Soto, A., S. Jacob, L., Patwa, R., Shah, H., Xu, K., et al. (2016) · Nature · doi:10.1038/nature18268 · Cited by 969 · see citing works
Epigenetic mechanisms of longevity and aging
Sen, P., Shah, P. P., Nativio, R., & Berger, S. L. (2016) · Cell · doi:10.1016/j.cell.2016.07.050 · Cited by 956 · see citing works
Self-citationCatastrophic nuclear envelope collapse in cancer cell micronuclei
Hatch, E. M., Fischer, A. H., Deerinck, T. J., & Hetzer, M. W. (2013) · Cell · doi:10.1016/j.cell.2013.06.007 · Cited by 741 · see citing works
Autophagy mediates degradation of nuclear lamina
Dou, Z., Xu, C., Donahue, G., Shimi, T., Pan, J.-A., Zhu, J., Ivanov, A., Capell, B. C., Drake, A. M., Shah, P. P., et al. (2015) · Nature · doi:10.1038/nature15548 · Cited by 655 · see citing works
Self-citationEpigenetic regulation of ageing: linking environmental inputs to genomic stability
Benayoun, B. A., Pollina, E. A., & Brunet, A. (2015) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm4048 · Cited by 610 · see citing works
Shah, P. P., Donahue, G., Otte, G. L., Capell, B. C., Nelson, D. M., Cao, K., Aggarwala, V., Cruickshanks, H. A., Rai, T. S., McBryan, T., et al. (2013) · Genes & Development · doi:10.1101/gad.223834.113 · Cited by 550 · see citing works
Self-citationThe role of nuclear lamin B1 in cell proliferation and senescence
Shimi, T., Butin-Israeli, V., Adam, S. A., Hamanaka, R. B., Goldman, A. E., Lucas, C. A., Shumaker, D. K., Kosak, S. T., Chandel, N. S., & Goldman, R. D. (2011) · Genes & Development · doi:10.1101/gad.179515.111 · Cited by 547 · see citing works
Lysosome-mediated processing of chromatin in senescence
Ivanov, A., Pawlikowski, J., Manoharan, I., van Tuyn, J., Nelson, D. M., Rai, T. S., Shah, P. P., Hewitt, G., Korolchuk, V. I., Passos, J. F., et al. (2013) · Journal of Cell Biology · doi:10.1083/jcb.201212110 · Cited by 539 · see citing works
Self-citationBRD4 Connects Enhancer Remodeling to Senescence Immune Surveillance
Tasdemir, N., Banito, A., Roe, J.-S., Alonso-Curbelo, D., Camiolo, M., Tschaharganeh, D. F., Huang, C.-H., Aksoy, O., Bolden, J. E., Chen, C.-C., et al. (2016) · Cancer Discovery · doi:10.1158/2159-8290.cd-16-0217 · Cited by 415 · see citing works
Sadaie, M., Salama, R., Carroll, T., Tomimatsu, K., Chandra, T., Young, A. R. J., Narita, M., Pérez-Mancera, P. A., Bennett, D. C., Chong, H., et al. (2013) · Genes & Development · doi:10.1101/gad.217281.113 · Cited by 323 · see citing works
STING Recognition of Cytoplasmic DNA Instigates Cellular Defense
Abe, T., Harashima, A., Xia, T., Konno, H., Konno, K., Morales, A. A., Ahn, J., Gutman, D. M., & Barber, G. N. (2013) · Molecular Cell · doi:10.1016/j.molcel.2013.01.039 · Cited by 300 · see citing works
Self-citationThe AIM2-like Receptors Are Dispensable for the Interferon Response to Intracellular DNA
Gray, E. E., Winship, D., Snyder, J. M., Child, S. J., Geballe, A. P., & Stetson, D. B. (2016) · Immunity · doi:10.1016/j.immuni.2016.06.015 · Cited by 183 · see citing works
MLL1 is essential for the senescence-associated secretory phenotype
Capell, B. C., Drake, A. M., Zhu, J., Shah, P. P., Dou, Z., Dorsey, J., Simola, D. F., Donahue, G., Sammons, M., Rai, T. S., et al. (2016) · Genes & Development · doi:10.1101/gad.271882.115 · Cited by 156 · see citing works
Self-citationChen, Y., Wang, L., Jin, J., Luan, Y., Chen, C., Yu, L., Chu, H., Wang, X., Liao, G., Yu, Y., et al. (2017) · The Journal of Experimental Medicine · doi:10.1084/jem.20161387 · Cited by 107 · see citing works
A genetic screen reveals Foxa3 and TNFR1 as key regulators of liver repopulationPreprint
Wangensteen, K. J., Zhang, S., Greenbaum, L. E., & Kaestner, K. H. (2015) · Genes & Development · doi:10.1101/gad.258855.115 · Cited by 45 · see citing works
Self-citationChIP-Sequencing to Map the Epigenome of Senescent Cells Using Benzonase Endonuclease
Rai, T. S., & Adams, P. D. (2016) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/bs.mie.2016.01.021 · Cited by 8 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Hallmarks of Cellular Senescence
Hernandez-Segura, A., Nehme, J., & Demaria, M. (2018) · Trends in Cell Biology · doi:10.1016/j.tcb.2018.02.001 · Cited by 2,605 · see citing works
The cGAS–STING pathway as a therapeutic target in inflammatory diseases
Decout, A., Katz, J. D., Venkatraman, S., & Ablasser, A. (2021) · Nature Reviews Immunology · doi:10.1038/s41577-021-00524-z · Cited by 2,309 · see citing works
Cellular senescence in ageing: from mechanisms to therapeutic opportunities
Di Micco, R., Krizhanovsky, V., Baker, D., & d’Adda di Fagagna, F. (2021) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-00314-w · Cited by 2,277 · see citing works
Molecular mechanisms and cellular functions of cGAS–STING signalling
Hopfner, K.-P., & Hornung, V. (2020) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-0244-x · Cited by 2,052 · see citing works
Aging and aging-related diseases: from molecular mechanisms to interventions and treatments
Guo, J., Huang, X., Dou, L., Yan, M., Shen, T., Tang, W., & Li, J. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01251-0 · Cited by 1,834 · see citing works
DAMP-sensing receptors in sterile inflammation and inflammatory diseases
Gong, T., Liu, L., Jiang, W., & Zhou, R. (2020) · Nature Reviews Immunology · doi:10.1038/s41577-019-0215-7 · Cited by 1,672 · see citing works
Chromosomal instability drives metastasis through a cytosolic DNA response
Bakhoum, S. F., Ngo, B., Laughney, A. M., Cavallo, J.-A., Murphy, C. J., Ly, P., Shah, P., Sriram, R. K., Watkins, T. B. K., Taunk, N. K., et al. (2018) · Nature · doi:10.1038/nature25432 · Cited by 1,638 · see citing works
Mechanisms of Cellular Senescence: Cell Cycle Arrest and Senescence Associated Secretory Phenotype
Kumari, R., & Jat, P. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.645593 · Cited by 1,622 · see citing works
The cGAS–cGAMP–STING pathway connects DNA damage to inflammation, senescence, and cancer
Li, T., & Chen, Z. J. (2018) · Journal of Experimental Medicine · doi:10.1084/jem.20180139 · Cited by 1,293 · see citing works
The Cytosolic DNA-Sensing cGAS–STING Pathway in Cancer
Kwon, J., & Bakhoum, S. F. (2020) · Cancer Discovery · doi:10.1158/2159-8290.cd-19-0761 · Cited by 1,293 · see citing works
Cellular Senescence: Aging, Cancer, and Injury
Calcinotto, A., Kohli, J., Zagato, E., Pellegrini, L., Demaria, M., & Alimonti, A. (2019) · Physiological Reviews · doi:10.1152/physrev.00020.2018 · Cited by 1,270 · see citing works
L1 drives IFN in senescent cells and promotes age-associated inflammation
De Cecco, M., Ito, T., Petrashen, A. P., Elias, A. E., Skvir, N. J., Criscione, S. W., Caligiana, A., Brocculi, G., Adney, E. M., Boeke, J. D., et al. (2019) · Nature · doi:10.1038/s41586-018-0784-9 · Cited by 1,255 · see citing works
“Cytoplasmic DNA can originate from several sources, such as mtDNA released from stressed mitochondria 28 or cytoplasmic chromatin fragments (CCF) released from damaged nuclei 29,30 .”
Senescence and aging: Causes, consequences, and therapeutic avenues
McHugh, D., & Gil, J. (2018) · Journal of Cell Biology · doi:10.1083/jcb.201708092 · Cited by 1,233 · see citing works
Mechanisms and functions of cellular senescence
Herranz, N., & Gil, J. (2018) · Journal of Clinical Investigation · doi:10.1172/jci95148 · Cited by 1,232 · see citing works
Senescence and the SASP: many therapeutic avenues
Birch, J., & Gil, J. (2020) · Genes & Development · doi:10.1101/gad.343129.120 · Cited by 1,177 · see citing works
Cellular senescence and senolytics: the path to the clinic
Chaib, S., Tchkonia, T., & Kirkland, J. L. (2022) · Nature Medicine · doi:10.1038/s41591-022-01923-y · Cited by 1,105 · see citing works
cGAS in action: Expanding roles in immunity and inflammation
Ablasser, A., & Chen, Z. J. (2019) · Science · doi:10.1126/science.aat8657 · Cited by 1,077 · see citing works
cGAS–STING drives ageing-related inflammation and neurodegeneration
Gulen, M. F., Samson, N., Keller, A., Schwabenland, M., Liu, C., Glück, S., Thacker, V. V., Favre, L., Mangeat, B., Kroese, L. J., et al. (2023) · Nature · doi:10.1038/s41586-023-06373-1 · Cited by 1,074 · see citing works
Mitochondrial dysfunction in cell senescence and aging
Miwa, S., Kashyap, S., Chini, E., & von Zglinicki, T. (2022) · Journal of Clinical Investigation · doi:10.1172/jci158447 · Cited by 1,061 · see citing works
Harnessing innate immunity in cancer therapy
Demaria, O., Cornen, S., Daëron, M., Morel, Y., Medzhitov, R., & Vivier, E. (2019) · Nature · doi:10.1038/s41586-019-1593-5 · Cited by 957 · see citing works
The senescence-associated secretory phenotype and its physiological and pathological implications
Wang, B., Han, J., Elisseeff, J. H., & Demaria, M. (2024) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-024-00727-x · Cited by 948 · see citing works
Ruysscher, D. D., Niedermann, G., Burnet, N. G., Siva, S., Lee, A. W. M., & Hegi‐Johnson, F. (2019) · Nature Reviews Disease Primers · doi:10.1038/s41572-019-0064-5 · Cited by 880 · see citing works
The complex role of tumor-infiltrating macrophages
Christofides, A., Strauss, L., Yeo, A. T., Cao, C., Charest, A., & Boussiotis, V. A. (2022) · Nature Immunology · doi:10.1038/s41590-022-01267-2 · Cited by 869 · see citing works
Unmasking senescence: context-dependent effects of SASP in cancer
Faget, D. V., Ren, Q., & Stewart, S. A. (2019) · Nature Reviews Cancer · doi:10.1038/s41568-019-0156-2 · Cited by 863 · see citing works
Structures and Mechanisms in the cGAS-STING Innate Immunity Pathway
Zhang, X., Bai, X., & Chen, Z. J. (2020) · Immunity · doi:10.1016/j.immuni.2020.05.013 · Cited by 845 · see citing works
The Multifaceted Role of Chromosomal Instability in Cancer and Its Microenvironment
Bakhoum, S. F. W., & Cantley, L. C. (2018) · Cell · doi:10.1016/j.cell.2018.08.027 · Cited by 717 · see citing works
The cGAS–STING pathway and cancer
Samson, N., & Ablasser, A. (2022) · Nature Cancer · doi:10.1038/s43018-022-00468-w · Cited by 705 · see citing works
Apoptotic stress causes mtDNA release during senescence and drives the SASP
Victorelli, S. G., Salmonowicz, H., Chapman, J., Martini, H., Vizioli, M. G., Riley, J. S., Cloix, C., Hall-Younger, E., Espíndola‐Netto, J. M., Jurk, D., et al. (2023) · Nature · doi:10.1038/s41586-023-06621-4 · Cited by 696 · see citing works
Self-citationDunphy, G., Flannery, S. M., Almine, J. F., Connolly, D. J., Paulus, C., Jønsson, K. L., Jakobsen, M. R., Nevels, M. M., Bowie, A. G., & Unterholzner, L. (2018) · Molecular Cell · doi:10.1016/j.molcel.2018.07.034 · Cited by 648 · see citing works
“cGAS can also detect DNA damage in a process involving mitotic progression, the formation of micronuclei and leakage of DNA into the cytosol, which occurs several days after recovery from DNA damage (Dou et al., 2017; Gl€ uck et al., 2017; Harding et al., 2017; Mackenzie et al., 2017).”
BackgroundcGAS-STING, an important pathway in cancer immunotherapy
Jiang, M., Chen, P., Wang, L., Li, W., Chen, B., Liu, Y., Wang, H., Zhao, S., Ye, L., He, Y., et al. (2020) · Journal of Hematology & Oncology · doi:10.1186/s13045-020-00916-z · Cited by 647 · see citing works
A guide to assessing cellular senescence <i>in vitro</i> and <i>in vivo</i>
González‐Gualda, E., Baker, A. G., Fruk, L., & Muñoz‐Espín, D. (2021) · The FEBS Journal · doi:10.1111/febs.15570 · Cited by 645 · see citing works
Cellular senescence: a key therapeutic target in aging and diseases
Zhang, L., Pitcher, L. E., Yousefzadeh, M. J., Niedernhofer, L. J., Robbins, P. D., & Zhu, Y. (2022) · Journal of Clinical Investigation · doi:10.1172/jci158450 · Cited by 631 · see citing works
The senescence-associated secretory phenotype and its regulation
Lopes-Paciencia, S., Saint-Germain, E., Rowell, M.-C., Ruiz, A. F., Kalegari, P., & Ferbeyre, G. (2019) · Cytokine · doi:10.1016/j.cyto.2019.01.013 · Cited by 601 · see citing works
The dynamic nature of senescence in cancer
Lee, S., & Schmitt, C. A. (2019) · Nature Cell Biology · doi:10.1038/s41556-018-0249-2 · Cited by 588 · see citing works
Combination Cancer Therapy with Immune Checkpoint Blockade: Mechanisms and Strategies
Patel, S. A., & Minn, A. J. (2018) · Immunity · doi:10.1016/j.immuni.2018.03.007 · Cited by 574 · see citing works
Emerging views of the nucleus as a cellular mechanosensor
Kirby, T. J., & Lammerding, J. (2018) · Nature Cell Biology · doi:10.1038/s41556-018-0038-y · Cited by 560 · see citing works
Embracing cancer complexity: Hallmarks of systemic disease
Swanton, C., Bernard, E., Abbosh, C., André, F., Auwerx, J. H., Balmain, A., Bar‐Sagi, D., Bernards, R., Bullman, S., DeGregori, J. V., et al. (2024) · Cell · doi:10.1016/j.cell.2024.02.009 · Cited by 555 · see citing works
Obesity-Induced Cellular Senescence Drives Anxiety and Impairs Neurogenesis
Ogrodnik, M., Zhu, Y., Langhi, L. G. P., Tchkonia, T., Krüger, P., Fielder, E., Victorelli, S., Ruswhandi, R. A., Giorgadze, N., Pirtskhalava, T., et al. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2018.12.008 · Cited by 536 · see citing works
Self-citationLinking cellular stress responses to systemic homeostasis
Galluzzi, L., Yamazaki, T., & Kroemer, G. (2018) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-018-0068-0 · Cited by 529 · see citing works
Myeloid immunosuppression and immune checkpoints in the tumor microenvironment
Nakamura, K., & Smyth, M. J. (2019) · Cellular and Molecular Immunology · doi:10.1038/s41423-019-0306-1 · Cited by 521 · see citing works
Immunological Mechanisms Responsible for Radiation-Induced Abscopal Effect
Rodriguez-Ruiz, M. E., Vanpouille‐Box, C., Melero, I., Formenti, S. C., & Demaria, S. (2018) · Trends in Immunology · doi:10.1016/j.it.2018.06.001 · Cited by 502 · see citing works
LINE1 Derepression in aged wild-type and SIRT6-deficient mice drives inflammation
Simon, M., Van Meter, M., Ablaeva, J., Ke, Z., Gonzalez, R. S., Taguchi, T., De Cecco, M., Leonova, K. I., Kogan, V., Helfand, S. L., et al. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2019.02.014 · Cited by 498 · see citing works
Glover, H. L., Schreiner, A., Dewson, G., & Tait, S. W. G. (2024) · Nature Cell Biology · doi:10.1038/s41556-024-01429-4 · Cited by 489 · see citing works
The ageing epigenome and its rejuvenation
Zhang, W., Qu, J. T., Liu, G., & Belmonte, J. C. I. (2020) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-019-0204-5 · Cited by 472 · see citing works
Cellular functions of cGAS-STING signaling
Chen, C., & Xu, P. (2022) · Trends in Cell Biology · doi:10.1016/j.tcb.2022.11.001 · Cited by 469 · see citing works
The role of retrotransposable elements in ageing and age-associated diseases
Gorbunova, V., Seluanov, A., Mita, P., McKerrow, W., Fenyö, D., Boeke, J. D., Linker, S. B., Gage, F. H., Kreiling, J. A., Petrashen, A. P., et al. (2021) · Nature · doi:10.1038/s41586-021-03542-y · Cited by 457 · see citing works
Ageing, Cellular Senescence and Neurodegenerative Disease
Kritsilis, M., V. Rizou, S., Koutsoudaki, P. N., Evangelou, K., Gorgoulis, V. G., & Papadopoulos, D. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19102937 · Cited by 448 · see citing works
AARS1 and AARS2 sense l-lactate to regulate cGAS as global lysine lactyltransferases
Li, H., Liu, C., Li, R., Zhou, L., Ran, Y., Yang, Q., Huang, H., Lu, H., Song, H., Yang, B., et al. (2024) · Nature · doi:10.1038/s41586-024-07992-y · Cited by 444 · see citing works
Cai, Y., Song, W., Li, J., Jing, Y., Liang, C., Zhang, L., Zhang, X., Zhang, W., Liu, B., An, Y., et al. (2022) · Science China Life Sciences · doi:10.1007/s11427-022-2161-3 · Cited by 436 · see citing works
Autophagy and the cell biology of age-related disease
Leidal, A. M., Levine, B., & Debnath, J. (2018) · Nature Cell Biology · doi:10.1038/s41556-018-0235-8 · Cited by 424 · see citing works
SenNet recommendations for detecting senescent cells in different tissues
Suryadevara, V., Hudgins, A. D., Rajesh, A., Pappalardo, A., Karpova, A., Dey, A. K., Hertzel, A., Agudelo, A., Rocha, A., Soygur, B., et al. (2024) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-024-00738-8 · Cited by 408 · see citing works
Self-citationThe Cytoplasmic DNA Sensor cGAS Promotes Mitotic Cell Death
Zierhut, C., Yamaguchi, N., Paredes, M. C. G., Luo, J., Carroll, T., & Funabiki, H. (2019) · Cell · doi:10.1016/j.cell.2019.05.035 · Cited by 403 · see citing works
Mechanisms and Regulation of Cellular Senescence
Roger, L., Tomas, F., & Gire, V. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222313173 · Cited by 395 · see citing works
DNA damage and repair in age-related inflammation
Zhao, Y., Simon, M. A., Seluanov, A., & Gorbunova, V. A. (2022) · Nature reviews. Immunology · doi:10.1038/s41577-022-00751-y · Cited by 393 · see citing works
Immune ageing at single-cell resolution
Mogilenko, D. A., Shchukina, I., & Artyomov, M. N. (2021) · Nature reviews. Immunology · doi:10.1038/s41577-021-00646-4 · Cited by 392 · see citing works
Bao, H., Cao, J., Chen, M., Min, C., Chen, W., Chen, X., Chen, Y., Chen, Y., Chen, Y., Chen, Z., et al. (2023) · Science China Life Sciences · doi:10.1007/s11427-023-2305-0 · Cited by 389 · see citing works
Structure of the Human cGAS–DNA Complex Reveals Enhanced Control of Immune Surveillance
Zhou, W., Whiteley, A. T., Mann, C. C. D. O., Morehouse, B. R., Nowak, R. P., Fischer, E. S., Gray, N. S., Mekalanos, J. J., & Kranzusch, P. J. (2018) · Cell · doi:10.1016/j.cell.2018.06.026 · Cited by 380 · see citing works
Molecular Mechanisms of Radiation-Induced Cancer Cell Death: A Primer
Sia, J., Szmyd, R., Hau, E., & Gee, H. E. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.00041 · Cited by 378 · see citing works
New frontiers in the cGAS-STING intracellular DNA-sensing pathway
Dvorkin, S., Cambier, S., Volkman, H. E., & Stetson, D. B. (2024) · Immunity · doi:10.1016/j.immuni.2024.02.019 · Cited by 377 · see citing works
Guidelines for minimal information on cellular senescence experimentation in vivo
Ogrodnik, M., Carlos Acosta, J., Adams, P. D., d’Adda di Fagagna, F., Baker, D. J., Bishop, C. L., Chandra, T., Collado, M., Gil, J., Gorgoulis, V., et al. (2024) · Cell · doi:10.1016/j.cell.2024.05.059 · Cited by 376 · see citing works
Self-citationCarozza, J. A., Böhnert, V., Nguyen, K. C., Skariah, G. M., Shaw, K. E., Brown, J. A., Rafat, M., von Eyben, R., Graves, E. E., Glenn, J. S., et al. (2020) · Nature Cancer · doi:10.1038/s43018-020-0028-4 · Cited by 363 · see citing works
Benayoun, B. A., Pollina, E. A., Singh, P. P., Mahmoudi, S., Harel, I., Casey, K. M., Dulken, B. W., Kundaje, A., & Brunet, A. (2019) · Genome Research · doi:10.1101/gr.240093.118 · Cited by 360 · see citing works
Vizioli, M. G., Liu, T., Miller, K. N., Robertson, N. A., Gilroy, K., Lagnado, A. B., Perez-Garcia, A., Kiourtis, C., Dasgupta, N., Lei, X., et al. (2020) · Genes & Development · doi:10.1101/gad.331272.119 · Cited by 359 · see citing works
Self-citationVirus-induced senescence is a driver and therapeutic target in COVID-19
Lee, S., Yu, Y., Trimpert, J., Benthani, F., Mairhofer, M., Richter-Pechanska, P., Wyler, E., Belenki, D., Kaltenbrunner, S., Pammer, M., et al. (2021) · Nature · doi:10.1038/s41586-021-03995-1 · Cited by 350 · see citing works
Takahashi, A., Loo, T. M., Okada, R., Kamachi, F., Watanabe, Y., Wakita, M., Watanabe, S., Kawamoto, S., Miyata, K., Barber, G. N., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-03555-8 · Cited by 350 · see citing works
Self-citationOduro, P. K., Zheng, X., Wei, J., Yang, Y., Wang, Y., Zhang, H., Liu, E., Gao, X., Du, M., & Wang, Q. (2021) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2021.05.011 · Cited by 349 · see citing works
YAP/TAZ activity in stromal cells prevents ageing by controlling cGAS–STING
Sladitschek, H. L., Guarnieri, A., Brumana, G., Zanconato, F., Battilana, G., Xiccato, R. L., Panciera, T., Forcato, M., Bicciato, S., Guzzardo, V., et al. (2022) · Nature · doi:10.1038/s41586-022-04924-6 · Cited by 346 · see citing works
Mutant p53 Suppresses Innate Immune Signaling to Promote Tumorigenesis
Ghosh, M., Saha, S., Bettke, J. A., Nagar, R., Parrales, A., Iwakuma, T., van der Velden, A. W. M., & Martinez, L. A. (2020) · Cancer Cell · doi:10.1016/j.ccell.2021.01.003 · Cited by 344 · see citing works
Regulation of cGAS- and RLR-mediated immunity to nucleic acids
Ablasser, A., & Hur, S. (2019) · Nature Immunology · doi:10.1038/s41590-019-0556-1 · Cited by 333 · see citing works
Mitochondrial DNA Release in Innate Immune Signaling
Newman, L. E., & Shadel, G. S. (2023) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-032620-104401 · Cited by 331 · see citing works
Mitochondrial dysfunction and cell senescence: deciphering a complex relationship
Chapman, J., Fielder, E., & Passos, J. F. (2019) · FEBS Letters · doi:10.1002/1873-3468.13498 · Cited by 325 · see citing works
Causes and consequences of micronuclei
Krupina, K., Goginashvili, A., & Cleveland, D. W. (2021) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2021.01.004 · Cited by 321 · see citing works
Non-cell-autonomous cancer progression from chromosomal instability
Li, J., Hubisz, M. J., Earlie, E. M., Paez, M. A. D., Hong, C., Varela, A., Lettera, E., Deyell, M., Tavora, B., Havel, J. J., et al. (2023) · Nature · doi:10.1038/s41586-023-06464-z · Cited by 321 · see citing works
DNA Damage and Cancer Immunotherapy: A STING in the Tale
Reisländer, T., Groelly, F. J., & Tarsounas, M. (2020) · Molecular Cell · doi:10.1016/j.molcel.2020.07.026 · Cited by 318 · see citing works
Borghesan, M., Fafián-Labora, J., Eleftheriadou, O., Carpintero-Fernández, P., Paez-Ribes, M., Vizcay-Barrena, G., Swisa, A., Kolodkin-Gal, D., Ximénez-Embún, P., Lowe, R., et al. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.05.095 · Cited by 315 · see citing works
“Non-cell autonomous (paracrine) senescence via the SASP has been previously described as an important mechanism during senescence (Acosta et al., 2013; Dou et al., 2017; Hoare et al., 2016; Nelson et al., 2012), although these studies do not discern between the effect of soluble factors and EVs.”
BackgroundRole of the cGAS–STING pathway in systemic and organ-specific diseases
Skopelja‐Gardner, S., An, J., & Elkon, K. B. (2022) · Nature Reviews Nephrology · doi:10.1038/s41581-022-00589-6 · Cited by 315 · see citing works
Metastasis and Immune Evasion from Extracellular cGAMP Hydrolysis
Li, J., Duran, M. A., Dhanota, N., Chatila, W. K., Bettigole, S. E., Kwon, J., Sriram, R. K., Humphries, M. P., Salto-Tellez, M., James, J. A., et al. (2021) · Cancer Discovery · doi:10.1158/2159-8290.cd-20-0387 · Cited by 312 · see citing works
Manganese-Based Nanoactivator Optimizes Cancer Immunotherapy via Enhancing Innate Immunity
Hou, L., Tian, C., Yan, Y., Zhang, L., Zhang, H., & Zhang, Z. (2020) · ACS Nano · doi:10.1021/acsnano.9b06111 · Cited by 311 · see citing works
Interconnections between Inflammageing and Immunosenescence during Ageing
Teissier, T., Boulanger, É., & Cox, L. S. (2022) · Cells · doi:10.3390/cells11030359 · Cited by 310 · see citing works
Ohtani, N. (2022) · Inflammation and Regeneration · doi:10.1186/s41232-022-00197-8 · Cited by 306 · see citing works
Tight nuclear tethering of cGAS is essential for preventing autoreactivity
Volkman, H. E., Cambier, S., Gray, E. E., & Stetson, D. B. (2019) · eLife · doi:10.7554/elife.47491 · Cited by 303 · see citing works
Molecular mechanisms of viral oncogenesis in humans
Krump, N. A., & You, J. (2018) · Nature Reviews Microbiology · doi:10.1038/s41579-018-0064-6 · Cited by 300 · see citing works
Targeting the DNA damage response in immuno-oncology: developments and opportunities
Chabanon, R. M., Rouanne, M., Lord, C. J., Soria, J., Pasero, P., & Postel-Vinay, S. C. (2021) · Nature reviews. Cancer · doi:10.1038/s41568-021-00386-6 · Cited by 300 · see citing works
Cellular senescence in development, regeneration and disease
Rhinn, M., Ritschka, B., & Keyes, W. M. (2019) · Development · doi:10.1242/dev.151837 · Cited by 296 · see citing works
Zhang, D., Liu, Y., Zhu, Y., Zhang, Q. Y., Guan, H., Liu, S., Chen, S., Chen, M., Chen, C., Liao, Z., et al. (2022) · Nature Cell Biology · doi:10.1038/s41556-022-00894-z · Cited by 295 · see citing works
Activation of innate immune cGAS-STING pathway contributes to Alzheimer’s pathogenesis in 5×FAD mice
Xie, X., Ma, G., Li, X., Zhao, J., Zhao, Z., & Zeng, J. (2023) · Nature Aging · doi:10.1038/s43587-022-00337-2 · Cited by 292 · see citing works
Cuollo, L., Antonangeli, F., Santoni, A., & Soriani, A. (2020) · Biology · doi:10.3390/biology9120485 · Cited by 291 · see citing works
STING inhibitors target the cyclic dinucleotide binding pocket
Hong, Z., Mei, J., Li, C., Bai, G., Maimaiti, M., Hu, H., Yu, W., Sun, L., Zhang, L., Cheng, D., et al. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2105465118 · Cited by 291 · see citing works
Tau Activation of Microglial cGAS–IFN Reduces MEF2C‐mediated Cognitive Resilience
Udeochu, J. C., Amin, S., Huang, Y., Fan, L., Torres, E. R. S., Carling, G. K., Liu, B., McGurran, H., Coronas-Samano, G., Kauwe, G., et al. (2023) · Nature Neuroscience · doi:10.1038/s41593-023-01315-6 · Cited by 289 · see citing works
Targeting senescent cells in translational medicine
Pàez‐Ribes, M., González‐Gualda, E., Doherty, G. J., & Muñoz‐Espín, D. (2019) · EMBO Molecular Medicine · doi:10.15252/emmm.201810234 · Cited by 289 · see citing works
Cytoplasmic DNA: sources, sensing, and role in aging and disease
Miller, K. N., Victorelli, S. G., Salmonowicz, H., Dasgupta, N., Liu, T., Passos, J. F., & Adams, P. D. (2021) · Cell · doi:10.1016/j.cell.2021.09.034 · Cited by 288 · see citing works
Self-citationRegulation of cGAS–STING signalling and its diversity of cellular outcomes
Zhang, Z., & Zhang, C. (2025) · Nature Reviews Immunology · doi:10.1038/s41577-024-01112-7 · Cited by 287 · see citing works
The Cyclopeptide Astin C Specifically Inhibits the Innate Immune CDN Sensor STING
Li, S., Hong, Z., Wang, Z., Li, F., Mei, J., Huang, L., Lou, X., Zhao, S., Song, L., Chen, W., et al. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.11.097 · Cited by 275 · see citing works
Self-citationWu, S., Zhang, Q., Zhang, F., Meng, F., Liu, S., Zhou, R., Wu, Q., Li, X., Shen, L., Huang, J., et al. (2019) · Nature Cell Biology · doi:10.1038/s41556-019-0352-z · Cited by 274 · see citing works
Research Advances in How the cGAS-STING Pathway Controls the Cellular Inflammatory Response
Wan, D., Jiang, W., & Hao, J. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.00615 · Cited by 270 · see citing works
Barnett, K. C., Coronas-Serna, J. M., Zhou, W., Ernandes, M. J., Cao, A., Kranzusch, P. J., & Kagan, J. C. (2019) · Cell · doi:10.1016/j.cell.2019.01.049 · Cited by 268 · see citing works
The impact of mitotic errors on cell proliferation and tumorigenesisPreprint
Levine, M. S., & Holland, A. J. (2018) · Genes & Development · doi:10.1101/gad.314351.118 · Cited by 268 · see citing works
Yan, M., Li, Y., Luo, Q., Zeng, W., Shao, X., Li, L., Wang, Q., Wang, D., Zhang, Y., Diao, H., et al. (2022) · Cell Death Discovery · doi:10.1038/s41420-022-01046-w · Cited by 267 · see citing works
Harnessing innate immune pathways for therapeutic advancement in cancer
Hu, A.-K., Sun, L., Lin, H., Liao, Y., Yang, H., & Mao, Y. Q. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01765-9 · Cited by 265 · see citing works
Farr, J. N., & Khosla, S. (2019) · Bone · doi:10.1016/j.bone.2019.01.015 · Cited by 263 · see citing works
- Authors
- Dou, Z., Ghosh, K., Vizioli, M. G., Zhu, J., Sen, P., Wangensteen, K. J., Simithy, J., Lan, Y., Lin, Y., Zhou, Z., Capell, B. C., Xu, C., Xu, M., Kieckhaefer, J. E., Jiang, T., Shoshkes-Carmel, M., Tanim, K. M. A. A., Barber, G. N., Seykora, J. T., Millar, S. E., Kaestner, K. H., Garcia, B. A., Adams, P. D., & Berger, S. L.
- Affiliations
- University of Pennsylvania (US)
- Cancer Research UK Scotland Institute (GB)
- Peking University (CN)
- Abramson Cancer Center (US)
- University of Miami (US)
- Sanford Burnham Prebys Medical Discovery Institute (US)
- Corresponding author
- Adams, Peter D.
- Berger, Shelley L.
- ORCID
- Venue
- Nature
- Published
- 2017-10
- Volume
- 550
- Issue
- 7676
- Pages
- 402-406
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC5850938
- OpenAlex
- W2762611634
- Cited by
- 1,335
- References
- 37
- Citations by year
- 2026: 177 · 2025: 157 · 2024: 184 · 2023: 156 · 2022: 174 · 2021: 158 · 2020: 127 · 2019: 115 · 2018: 75 · 2017: 10
- FWCI
- 40.47
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- National Institutes of Health (CA078831)
- National Institute on Aging (K99AG053406, P01AG031862)
- National Cancer Institute (P01CA196539, R01CA078831)
- National Institute of Allergy and Infectious Diseases (R01AI079336)
- National Institute of Diabetes and Digestive and Kidney Diseases (K08DK106478)
- National Institute of Environmental Health Sciences (P30ES013508)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (K08AR070289, P30AR069589, T32AR007465)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- cGAS-STING pathway, cytosolic DNA sensing, cellular senescence, senescence-associated secretory phenotype, chronic inflammation, tumor surveillance, oncogenic Ras, ionizing radiation, innate immunity, tumor inflammation
- MeSH terms
- STING Protein, Cyclic Guanosine Monophosphate-Adenosine Monophosphate Synthase, Animals, Chromatin, Cytoplasm, Female, Humans, Immunity, Innate, Inflammation, Liver, Male, Membrane Proteins, Neoplasms, Nucleotidyltransferases, Radiation, Ionizing, Oncogene Protein p21(ras), Cytokines, Cellular Senescence, Cell Line, Tumor, Mice
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Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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