cGAS is essential for cellular senescence
Open accessAbstract
Significance: Cellular senescence is important for the maintenance of tissue homeostasis. Dysregulation of senescence is linked to many human diseases, such as cancer, premature aging, and age-related diseases. Although DNA damage response has been linked to senescence, the underlying mechanism is unknown. Here we show that cGAS is essential for the senescence phenotypes, including expression of inflammatory genes. This finding reveals a molecular mechanism of cellular senescence and suggests that modulation of cGAS activity may be a new strategy to treat senescence-associated human diseases that potentially include cancer, neurodegenerative diseases, cardiovascular diseases, and aging.
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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 [113]
The Results report that cGAS is required for induction of most SASP genes by DNA-damaging agents in human and mouse cells. The introduction describes STING activating NF-κB and IRF3, but the paper does not establish that STING regulates the SASP through those factors. Indeed, the Results report that STING loss did not accelerate spontaneous immortalization, suggesting a STING-independent role for cGAS. (LLM, conf=0.87)
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 [6]
The paper’s Discussion states that cGAS is essential for cellular senescence. But the Results section reports that STING deletion did not accelerate spontaneous immortalization and suggests that cGAS may act through a STING-independent mechanism. Thus, the paper supports a role for cGAS, but not an unqualified role for the cGAS–STING pathway in regulating senescence. (LLM, conf=0.87)
Experimental — accuracy not yet measuredThe cGAS-STING signaling pathway has recently been identified as a SASP regulator.
“The antiviral cyclic GMP‐AMP synthase (cGAS)‐stimulator of interferon genes (STING) signaling pathway has recently been identified as a SASP regulator.62, 63, 64”
From Cellular senescence and senescence-associated secretory phenotype via the cGAS-STING signaling pathway in cancer (2020) · cites this paper as [63]
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 Yang 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 [6]
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 Yang et al., 2017
The senescence-associated secretory phenotype is dependent on p38MAPK, NF-κB, cGAS/STING, NOTCH and mTOR signalling.
“Another key feature of cellular senescence is the senescence-associated secretory phenotype (SASP), which is dependent on p38MAPK (p38 mitogen-activated protein kinases), NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells), cGAS(cyclic GMP-AMP synthase)/STING(stimulator of IFN genes), NOTCH and mTORmammalian target of rapamycin) signalling [38,39,40,41,42].”
From Ageing, Cellular Senescence and Neurodegenerative Disease (2018) · cites this paper as [42]
DNA leakage from the senescent nucleus into the cytoplasm and consequent activation of the cGAS-STING anti-viral pathway is a mechanism of SASP onset.
“Recent data suggest DNA leakage from the senescent nucleus into the cytoplasm and consequent activation of the GMP-AMP Synthase-Stimulator of Interferon Genes (cGAS-STING) anti-viral pathway as a mechanism of SASP onset.146,147”
From Senescence-induced inflammation: an important player and key therapeutic target in atherosclerosis (2020) · cites this paper as [146]
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 [173]
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 [173]
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 [173]
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Cites
The serial cultivation of human diploid cell strains
Hayflick, L., & Moorhead, P. S. (1961) · Experimental Cell Research · doi:10.1016/0014-4827(61)90192-6 · Cited by 8,508 · see citing works
A biomarker that identifies senescent human cells in culture and in aging skin in vivo.
Dimri, G. P., Lee, X., Basile, G., Acosta, M., Scott, G., Roskelley, C., Medrano, E. E., Linskens, M., Rubelj, I., & Pereira-Smith, O. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.20.9363 · Cited by 7,477 · see citing works
Genome-scale CRISPR-Cas9 knockout screening in human cells
Shalem, O., Sanjana, N. E., Hartenian, E., Shi, X., Scott, D. A., Mikkelsen, T. S., Heckl, D., Ebert, B. L., Root, D. E., Doench, J. G., et al. (2014) · Science · doi:10.1126/science.1247005 · Cited by 5,234 · see citing works
The senescence-associated secretory phenotype: the dark side of tumor suppression
Coppé, J.-P., Desprez, P.-Y., Krtolica, A., & Campisi, J. (2010) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev-pathol-121808-102144 · Cited by 5,206 · see citing works
Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a
Serrano, M., Lin, A. W., McCurrach, M. E., Beach, D., & Lowe, S. W. (1997) · Cell · doi:10.1016/s0092-8674(00)81902-9 · Cited by 5,178 · cited 1× · see citing works
“At the molecular level, the p53p21 and pRb-p16 tumor suppressor pathways have been reported to be key mechanisms that control the execution and maintenance of senescence (8, 9).”
BackgroundCyclic 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
Self-citationCellular senescence: when bad things happen to good cells
Campisi, J., & d'Adda di Fagagna, F. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2233 · Cited by 4,441 · see citing works
Aging, Cellular Senescence, and Cancer
Campisi, J. (2013) · Annual Review of Physiology · doi:10.1146/annurev-physiol-030212-183653 · Cited by 2,954 · cited 2× · see citing works
“C senescence is a state of irreversible cell cycle arrest triggered by various types of cellular and environmental stress, such as telomere shortening, oncogene activation, and DNA damage (1, 2).”
BackgroundNaturally occurring p16Ink4a-positive cells shorten healthy lifespan
Baker, D. J., Childs, B. G., Durik, M., Wijers, M. E., Sieben, C. J., Zhong, J., A. Saltness, R., Jeganathan, K. B., Verzosa, G. C., Pezeshki, A., et al. (2016) · Nature · doi:10.1038/nature16932 · Cited by 2,891 · see citing works
Todaro, G. J., & Green, H. (1963) · The Journal of Cell Biology · doi:10.1083/jcb.17.2.299 · Cited by 2,725 · see citing works
Cyclic 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
Self-citationSenescence and tumour clearance is triggered by p53 restoration in murine liver carcinomas
Xue, W., Zender, L., Miething, C., Dickins, R. A., Hernando, E., Krizhanovsky, V., Cordon-Cardo, C., & Lowe, S. W. (2007) · Nature · doi:10.1038/nature05529 · Cited by 2,473 · see citing works
Cellular senescence in aging and age-related disease: from mechanisms to therapy
Childs, B. G., Durik, M., Baker, D. J., & van Deursen, J. M. (2015) · Nature Medicine · doi:10.1038/nm.4000 · Cited by 2,363 · see citing works
BRAFE600-associated senescence-like cell cycle arrest of human naevi
Michaloglou, C., Vredeveld, L. C. W., Soengas, M. S., Denoyelle, C., Kuilman, T., van der Horst, C. M. A. M., Majoor, D. M., Shay, J. W., Mooi, W. J., & Peeper, D. S. (2005) · Nature · doi:10.1038/nature03890 · Cited by 2,160 · see citing works
Oncogene-Induced Senescence Relayed by an Interleukin-Dependent Inflammatory Network
Kuilman, T., Michaloglou, C., Vredeveld, L. C. W., Douma, S., van Doorn, R., Desmet, C. J., Aarden, L. A., Mooi, W. J., & Peeper, D. S. (2008) · Cell · doi:10.1016/j.cell.2008.03.039 · Cited by 2,086 · see citing works
The essence of senescence: Figure 1.
Kuilman, T., Michaloglou, C., Mooi, W. J., & Peeper, D. S. (2010) · Genes & Development · doi:10.1101/gad.1971610 · Cited by 2,038 · see citing works
Čermák, T., Doyle, E., Christian, M. L., Wang, L., Zhang, Y., Schmidt, C. L., Baller, J. A., Somia, N. V., Bogdanove, A. J., & Voytas, D. F. (2011) · Nucleic Acids Research · doi:10.1093/nar/gkr218 · Cited by 2,034 · see citing works
DNA Topoisomerases and Their Poisoning by Anticancer and Antibacterial Drugs
Pommier, Y. G., Leo, E., Zhang, H., & Marchand, C. (2010) · Chemistry & Biology · doi:10.1016/j.chembiol.2010.04.012 · Cited by 1,842 · see citing works
Chemokine signaling via the CXCR2 receptor reinforces senescence
Acosta, J. C., O'Loghlen, A., Banito, A., Guijarro, M. V., Augert, A., Raguz, S., Fumagalli, M., Da Costa, M., Brown, C., Popov, N., et al. (2008) · Cell · doi:10.1016/j.cell.2008.03.038 · Cited by 1,801 · cited 1× · see citing works
“Interleukin 6 (IL6) and IL8, two key components of SASP, reinforce the senescence growth arrest in neighboring cells (14, 15).”
BackgroundGyőrffy, B., Surowiak, P., Budczies, J., & Lánczky, A. (2013) · PLoS ONE · doi:10.1371/journal.pone.0082241 · Cited by 1,763 · see citing works
Senescence in premalignant tumours
Collado, M., Gil, J., Efeyan, A., Guerra, C., Schuhmacher, A. J., Barradas, M., Benguría, A., Zaballos, A., Flores, J. M., Barbacid, M., et al. (2005) · Nature · doi:10.1038/436642a · Cited by 1,482 · see citing works
Senescent intimal foam cells are deleterious at all stages of atherosclerosis
Childs, B. G., Baker, D. J., Wijshake, T., Conover, C. A., Campisi, J., & van Deursen, J. M. (2016) · Science · doi:10.1126/science.aaf6659 · Cited by 1,195 · see citing works
RNA Polymerase III Detects Cytosolic DNA and Induces Type I Interferons through the RIG-I Pathway
Chiu, Y., MacMillan, J. B., & Chen, Z. J. (2009) · Cell · doi:10.1016/j.cell.2009.06.015 · Cited by 1,185 · see citing works
Self-citationSenescence in tumours: evidence from mice and humans
Collado, M., & Serrano, M. (2010) · Nature Reviews Cancer · doi:10.1038/nrc2772 · Cited by 1,124 · see citing works
Oxygen sensitivity severely limits the replicative lifespan of murine fibroblasts
Parrinello, S., Samper, E., Krtolica, A., Goldstein, J., Melov, S., & Campisi, J. (2003) · Nature Cell Biology · doi:10.1038/ncb1024 · Cited by 1,116 · see citing works
Pivotal Roles of cGAS-cGAMP Signaling in Antiviral Defense and Immune Adjuvant Effects
Li, X.-D., Wu, J., Gao, D., Wang, H., Sun, L., & Chen, Z. J. (2013) · Science · doi:10.1126/science.1244040 · Cited by 1,097 · see citing works
Self-citationChien, 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
Recognition of Cytosolic DNA Activates an IRF3-Dependent Innate Immune Response
Stetson, D. B., & Medzhitov, R. M. (2006) · Immunity · doi:10.1016/j.immuni.2005.12.003 · Cited by 1,003 · see citing works
Tumor Suppression in the Absence of p53-Mediated Cell-Cycle Arrest, Apoptosis, and Senescence
Li, T., Kon, N., Jiang, L., Tan, M., Ludwig, T., Zhao, Y., Baer, R., & Gu, W. (2012) · Cell · doi:10.1016/j.cell.2012.04.026 · Cited by 912 · see citing works
Senescence-messaging secretome: SMS-ing cellular stress
Kuilman, T., & Peeper, D. S. (2009) · Nature Reviews Cancer · doi:10.1038/nrc2560 · Cited by 909 · see citing works
Senescence of human fibroblasts induced by oncogenic Raf
Zhu, J., Woods, D., McMahon, M., & Bishop, J. M. (1998) · Genes & Development · doi:10.1101/gad.12.19.2997 · Cited by 826 · see citing works
A role for both RB and p53 in the regulation of human cellular senescence*1
SHAY, J. (1991) · Experimental Cell Research · doi:10.1016/0014-4827(91)90453-2 · Cited by 757 · see citing works
Sherr, C. J., & DePinho, R. A. (2000) · Cell · doi:10.1016/s0092-8674(00)00046-5 · Cited by 745 · see citing works
Härtlova, A., Erttmann, S. F., Raffi, F. A., Schmalz, A. M., Resch, U., Anugula, S., Lienenklaus, S., Nilsson, L. M., Kröger, A., Nilsson, J. A., et al. (2015) · Immunity · doi:10.1016/j.immuni.2015.01.012 · Cited by 716 · see citing works
Activation of cyclic GMP-AMP synthase by self-DNA causes autoimmune diseases
Gao, D., Li, T., Li, X.-D., Chen, X., Li, Q., Wight‐Carter, M., & Chen, Z. J. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1516465112 · Cited by 685 · see citing works
Self-citation(2002) · PubMed · Cited by 640 · see citing works
Kortlever, R. M., Higgins, P. J., & Bernards, R. (2006) · Nature Cell Biology · doi:10.1038/ncb1448 · Cited by 637 · cited 1× · see citing works
“Components of SASP not only serve as a marker of senescence, but also participate in the senescence process (13).”
BackgroundXia, T., Konno, H., Ahn, J., & Barber, G. N. (2016) · Cell Reports · doi:10.1016/j.celrep.2015.12.029 · Cited by 589 · see citing works
cGAS is essential for the antitumor effect of immune checkpoint blockade
Wang, H., Hu, S., Chen, X., Shi, H., Chen, C., Sun, L., & Chen, Z. J. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1621363114 · Cited by 563 · see citing works
Self-citationSauer, J., Troha, K., von Moltke, J., Monroe, K. M., Rae, C. S., Brubaker, S. W., Hyodo, M., Hayakawa, Y., Woodward, J. J., Portnoy, D. A., et al. (2010) · Infection and Immunity · doi:10.1128/iai.00999-10 · Cited by 540 · 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
Zhang, X., Wu, J., Du, F., Xu, H., Sun, L., Chen, Z., Brautigam, C. A., Zhang, X., & Chen, Z. J. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.01.003 · Cited by 507 · see citing works
Self-citationGehrke, N., Mertens, C., Zillinger, T., Wenzel, J., Bald, T., Zahn, S., Tüting, T., Hartmann, G., & Barchet, W. (2013) · Immunity · doi:10.1016/j.immuni.2013.08.004 · Cited by 476 · see citing works
BRD4 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
Gray, E. E., Treuting, P. M., Woodward, J. J., & Stetson, D. B. (2015) · The Journal of Immunology · doi:10.4049/jimmunol.1500969 · Cited by 384 · see citing works
Coppé, J.-P., Patil, C. K., Rodier, F., Sun, Y., Muñoz, D. P., Goldstein, J., Nelson, P. S., Desprez, P.-Y., & Campisi, J. (2008) · PLoS Biology · doi:10.1371/journal.pbio.0060301 · Cited by 302 · see citing works
Cellular senescence in vivo: a barrier to tumorigenesis
Prieur, A., & Peeper, D. S. (2008) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2008.01.007 · Cited by 260 · see citing works
DNA damage-induced type I interferon promotes senescence and inhibits stem cell function
Yu, Q., Katlinskaya, Y. V., Carbone, C. J., Zhao, B., Katlinski, K. V., Zheng, H., Guha, M., Li, N., Chen, Q., Yang, T., et al. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.03.069 · Cited by 260 · see citing works
Self-citationDnase2a deficiency uncovers lysosomal clearance of damaged nuclear DNA via autophagy
Lan, Y. Y., Londoño, D., Bouley, R., Rooney, M. S., & Hacohen, N. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.08.074 · Cited by 236 · see citing works
Takahashi, A., Imai, Y., Yamakoshi, K., Kuninaka, S., Ohtani, N., Yoshimoto, S., Hori, S., Tachibana, M., Anderton, E., Takeuchi, T., et al. (2012) · Molecular Cell · doi:10.1016/j.molcel.2011.10.018 · Cited by 205 · 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
Opposing roles of NF-κB in anti-cancer treatment outcome unveiled by cross-species investigationsPreprint
Hua, J., Kase, J., Dörr, J. R., Milanovic, M., Lenze, D., Grau, M., Beuster, G., Ji, S., Reimann, M., Lenz, P., et al. (2011) · Genes & Development · doi:10.1101/gad.17620611 · Cited by 99 · see citing works
Stress-induced premature senescence in BJ and hTERT-BJ1 human foreskin fibroblasts
de Magalhães, J. P., Chainiaux, F., Remacle, J., & Toussaint, O. (2002) · FEBS Letters · doi:10.1016/s0014-5793(02)02973-3 · Cited by 90 · see citing works
Modulation of therapy-induced senescence by reactive lipid aldehydes
Flor, A. C., Doshi, A. P., & Kron, S. J. (2016) · Cell Death Discovery · doi:10.1038/cddiscovery.2016.45 · Cited by 40 · see citing works
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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
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
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
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
DNA sensing by the cGAS–STING pathway in health and disease
Motwani, M., Pesiridis, S., & Fitzgerald, K. A. (2019) · Nature Reviews Genetics · doi:10.1038/s41576-019-0151-1 · Cited by 1,467 · 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
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
Self-citationCytoplasmic chromatin triggers inflammation in senescence and cancer
Dou, Z., Ghosh, K., Vizioli, M. G., Zhu, J., Sen, P., Wangensteen, K. J., Simithy, J., Lan, Y., Lin, Y., Zhou, Z., et al. (2017) · Nature · doi:10.1038/nature24050 · Cited by 1,335 · 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
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
“The cGAS/STING pathway is considered a key regulator of SASP induction (Dou et al. 2017; Glück et al. 2017; Yang et al. 2017).”
BackgroundcGAS–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
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
Exploiting senescence for the treatment of cancer
Wang, L., Lankhorst, L., & Bernards, R. (2022) · Nature Reviews Cancer · doi:10.1038/s41568-022-00450-9 · Cited by 867 · 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
cGAS-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
Self-citationThe 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
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
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
Strategies for targeting senescent cells in human disease
Gasek, N. S., Kuchel, G. A., Kirkland, J. L., & Xu, M. (2021) · Nature Aging · doi:10.1038/s43587-021-00121-8 · Cited by 501 · see citing works
Senescent cell clearance by the immune system: Emerging therapeutic opportunities
Prata, L. G. P. L., Ovsyannikova, I. G., Tchkonia, T., & Kirkland, J. L. (2018) · Seminars in Immunology · doi:10.1016/j.smim.2019.04.003 · Cited by 497 · 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
Chronic inflammation and the hallmarks of aging
Baechle, J. J., Chen, N., Makhijani, P., Winer, S., Furman, D., & Winer, D. A. (2023) · Molecular Metabolism · doi:10.1016/j.molmet.2023.101755 · Cited by 471 · see citing works
Huang, L. S., Hong, Z., Wu, W., Xiong, S., Zhong, M., Gao, X., Rehman, J., & Malik, A. B. (2020) · Immunity · doi:10.1016/j.immuni.2020.02.002 · Cited by 435 · 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
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
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
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
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
“, 2013) and by the cGAS-STING (cyclic guanosine monophosphate [GMP]-AMP synthase linked to the stimulator of IFN genes) pathway (Dou et al., 2017; Gl€ uck et al., 2017; Yang et al., 2017).”
BackgroundMetastasis 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
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
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
Lama, L., Adura, C., Xie, W., Tomita, D., Kamei, T., Kuryavyi, V., Gogakos, T., Steinberg, J. I., Miller, M., Ramos-Espiritu, L., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-08620-4 · Cited by 303 · 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
Cuollo, L., Antonangeli, F., Santoni, A., & Soriani, A. (2020) · Biology · doi:10.3390/biology9120485 · Cited by 291 · 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
Markers of T Cell Senescence in Humans
Xu, W., & Larbi, A. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18081742 · Cited by 261 · see citing works
Cytosolic DNA Sensing in Organismal Tumor Control
Vanpouille-Box, C., Demaria, S., Formenti, S. C., & Galluzzi, L. (2018) · Cancer Cell · doi:10.1016/j.ccell.2018.05.013 · Cited by 250 · see citing works
Structural basis for the inhibition of cGAS by nucleosomes
Kujirai, T., Zierhut, C., Takizawa, Y., Kim, R., Negishi, L., Uruma, N., Hirai, S., Funabiki, H., & Kurumizaka, H. (2020) · Science · doi:10.1126/science.abd0237 · Cited by 243 · see citing works
STING mediates neurodegeneration and neuroinflammation in nigrostriatal α-synucleinopathy
Hinkle, J. T., Patel, J., Panicker, N., Karuppagounder, S. S., Biswas, D., Belingon, B., Chen, R., Brahmachari, S., Pletnikova, O., Troncoso, J. C., et al. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2118819119 · Cited by 240 · see citing works
Loo, T. M., Miyata, K., Tanaka, Y., & Takahashi, A. (2020) · Cancer Science · doi:10.1111/cas.14266 · Cited by 232 · see citing works
Cellular senescence: Immunosurveillance and future immunotherapy
Burton, D. G. A., & Stolzing, A. (2018) · Ageing Research Reviews · doi:10.1016/j.arr.2018.02.001 · Cited by 221 · see citing works
Cellular senescence: the sought or the unwanted?
Sun, Y., Coppé, J.-P., & Lam, E. W.-F. (2018) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2018.08.002 · Cited by 208 · see citing works
Inflammation and DNA damage: cause, effect or both
Pezone, A., Olivieri, F., Napoli, M. V., Procopio, A., Avvedimento, E. V., & Gabrielli, A. (2023) · Nature Reviews Rheumatology · doi:10.1038/s41584-022-00905-1 · Cited by 212 · see citing works
Role of the cGAS–STING pathway in cancer development and oncotherapeutic approaches
Khoo, L. T., & Chen, L. (2018) · The EMBO Reports · doi:10.15252/embr.201846935 · Cited by 204 · see citing works
cGAS-mediated induction of type I interferon due to inborn errors of histone pre-mRNA processing
Uggenti, C., Lepelley, A., Depp, M., Badrock, A. P., Rodero, M. P., El-Daher, M.-T., Rice, G. I., Dhir, S., Wheeler, A. P., Dhir, A., et al. (2020) · Nature Genetics · doi:10.1038/s41588-020-00737-3 · Cited by 192 · see citing works
Senescent Cells: Emerging Targets for Human Aging and Age-Related Diseases
Song, S., Lam, E. W.-F., Tchkonia, T., Kirkland, J. L., & Sun, Y. (2020) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2020.03.008 · Cited by 195 · see citing works
Senescence in the pathogenesis of age-related macular degeneration
Blasiak, J. (2020) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-019-03420-x · Cited by 183 · see citing works
Connecting aging biology and inflammation in the omics era
Walker, K. A., Basisty, N., Wilson, D. M., & Ferrucci, L. (2022) · Journal of Clinical Investigation · doi:10.1172/jci158448 · Cited by 189 · see citing works
Senescence-induced inflammation: an important player and key therapeutic target in atherosclerosis
Stojanović, S. D., Fiedler, J., Bauersachs, J., Thum, T., & Sedding, D. G. (2020) · European Heart Journal · doi:10.1093/eurheartj/ehz919 · Cited by 188 · see citing works
The World Goes Bats: Living Longer and Tolerating Viruses
Gorbunova, V., Seluanov, A., & Kennedy, B. K. (2020) · Cell Metabolism · doi:10.1016/j.cmet.2020.06.013 · Cited by 162 · see citing works
p53 engages the cGAS/STING cytosolic DNA sensing pathway for tumor suppression
Ghosh, M., Saha, S., Li, J., Montrose, D. C., & Martinez, L. A. (2023) · Molecular Cell · doi:10.1016/j.molcel.2022.12.023 · Cited by 166 · see citing works
Mechanism and therapeutic potential of targeting cGAS-STING signaling in neurological disorders
Huang, Y., Liu, B., Sinha, S. C., Amin, S., & Gan, L. (2023) · Molecular Neurodegeneration · doi:10.1186/s13024-023-00672-x · Cited by 164 · see citing works
Senescence and senotherapeutics: a new field in cancer therapy
Myrianthopoulos, V., Evangelou, K., Vasileiou, P. V. S., Cooks, T., Vassilakopoulos, T. P., Pangalis, G. A., Kouloukoussa, M., Kittas, C., Georgakilas, A. G., & Gorgoulis, V. G. (2019) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2018.08.006 · Cited by 160 · see citing works
Cyclic GMP-AMP synthase promotes the inflammatory and autophagy responses in Huntington disease
Sharma, M., Rajendrarao, S., Shahani, N., Ramírez-Jarquín, U. N., & Subramaniam, S. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2002144117 · Cited by 155 · see citing works
The role of cellular senescence and SASP in tumour microenvironment
Takasugi, M., Yoshida, Y., Hara, E., & Ohtani, N. (2023) · The FEBS Journal · doi:10.1111/febs.16381 · Cited by 144 · see citing works
FoxM1 repression during human aging leads to mitotic decline and aneuploidy-driven full senescence
Macedo, J. C., Vaz, S., Bakker, B., Ribeiro, R., Bakker, P. L., Escandell, J. M., Ferreira, M. G., Medema, R., Foijer, F., & Logarinho, E. (2018) · Nature Communications · doi:10.1038/s41467-018-05258-6 · Cited by 131 · see citing works
Extranuclear DNA accumulates in aged cells and contributes to senescence and inflammation
Lan, Y. Y., Heather, J. M., Eisenhaure, T., Garris, C. S., Lieb, D., Raychowdhury, R., & Hacohen, N. (2019) · Aging Cell · doi:10.1111/acel.12901 · Cited by 130 · see citing works
Mechanisms of DNA damage-mediated neurotoxicity in neurodegenerative disease
Welch, G., & Tsai, L. (2022) · The EMBO Reports · doi:10.15252/embr.202154217 · Cited by 129 · see citing works
Cytosolic sensing of immuno-stimulatory DNA, the enemy within
Dhanwani, R., Takahashi, M., & Sharma, S. (2018) · Current Opinion in Immunology · doi:10.1016/j.coi.2017.11.004 · Cited by 123 · see citing works
Lau, L., Porciuncula, A., Yu, A., Iwakura, Y., & David, G. (2019) · Molecular and Cellular Biology · doi:10.1128/mcb.00586-18 · Cited by 119 · see citing works
Oncogene-induced senescence: From biology to therapy
Zhu, H., Blake, S., Kusuma, F. K., Pearson, R. B., Kang, J., & Chan, K. T. (2020) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2020.111229 · Cited by 116 · see citing works
Chen, J., Harding, S. M., Natesan, R., Tian, L., Benci, J. L., Li, W., Minn, A. J., Asangani, I. A., & Greenberg, R. A. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.108080 · Cited by 111 · see citing works
TBK1, a central kinase in innate immune sensing of nucleic acids and beyond
Zhou, R., Zhang, Q., & Xu, P. (2020) · Acta Biochimica et Biophysica Sinica · doi:10.1093/abbs/gmaa051 · Cited by 104 · see citing works
Targeting senescent cells for a healthier longevity: the roadmap for an era of global aging
Sun, Y., Li, Q., & Kirkland, J. L. (2022) · Life Medicine · doi:10.1093/lifemedi/lnac030 · Cited by 105 · see citing works
A Nuclear Export Signal Is Required for cGAS to Sense Cytosolic DNA
Sun, H., Huang, Y., Mei, S., Xu, F., Liu, X., Zhao, F., Yin, L., Zhang, D., Wei, L., Wu, C., et al. (2021) · Cell Reports · doi:10.1016/j.celrep.2020.108586 · Cited by 105 · see citing works
Cancer-associated adipocytes as immunomodulators in cancer
Wu, Q., Li, B., Li, J., Sun, S., Yuan, J., & Sun, S. (2021) · Biomarker Research · doi:10.1186/s40364-020-00257-6 · Cited by 105 · see citing works
Metabolomic profiling of single enlarged lysosomes
Zhu, H., Li, Q., Liao, T., Yin, X., Chen, Q., Wang, Z., Dai, M., Yi, L., Ge, S., Miao, C., et al. (2021) · Nature Methods · doi:10.1038/s41592-021-01182-8 · Cited by 103 · see citing works
Self-citationChung, S., Jeong, J.-H., Park, J.-C., Han, J. W., Lee, Y., Kim, J.-I., & Mook-Jung, I. (2024) · Experimental & Molecular Medicine · doi:10.1038/s12276-024-01295-y · Cited by 103 · see citing works
“Although its cellular localization is divergent, cGAS often colocalizes with the DNA damage marker γ H2AX under certain stress conditions 29 .”
Hepatic senescence, the good and the bad
Huda, N., Liu, G., Hong, H., Yan, S., Khambu, B., & Yin, X.-M. (2019) · World Journal of Gastroenterology · doi:10.3748/wjg.v25.i34.5069 · Cited by 100 · see citing works
Chromatin basis of the senescence-associated secretory phenotype
Hao, X., Wang, C., & Zhang, R. (2022) · Trends in Cell Biology · doi:10.1016/j.tcb.2021.12.003 · Cited by 94 · see citing works
Thadathil, N., Delotterie, D. F., Xiao, J., Hori, R., McDonald, M. P., & Khan, M. M. (2021) · Molecular Neurobiology · doi:10.1007/s12035-020-02109-8 · Cited by 94 · see citing works
CGAS is a micronucleophagy receptor for the clearance of micronuclei
Zhao, M., Wang, F., Wu, J., Cheng, Y., Cao, Y., Wu, X., Ma, M., Tang, F., Liu, Z., Liu, H., et al. (2021) · Autophagy · doi:10.1080/15548627.2021.1899440 · Cited by 89 · see citing works
DNA damage-induced immune response: Micronuclei provide key platform
Gekara, N. O. (2017) · Journal of Cell Biology · doi:10.1083/jcb.201708069 · Cited by 88 · see citing works
Short-term gain, long-term pain: the senescence life cycle and cancer
Chan, A. S. L., & Narita, M. (2019) · Genes & Development · doi:10.1101/gad.320937.118 · Cited by 80 · see citing works
Miyata, K., Imai, Y., Hori, S., Nishio, M., Loo, T. M., Okada, R., Yang, L., Nakadai, T., Maruyama, R., Fujii, R., et al. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2025647118 · Cited by 74 · see citing works
DOT1L modulates the senescence-associated secretory phenotype through epigenetic regulation of IL1A
Leon, K. E., Buj, R., Lesko, E., Dahl, E. S., Chen, C.-W., Tangudu, N. K., Imamura-Kawasawa, Y., Kossenkov, A. V., Hobbs, R. P., & Aird, K. M. (2021) · Journal of Cell Biology · doi:10.1083/jcb.202008101 · Cited by 70 · see citing works
Cytoplasmic chromatin fragments-from mechanisms to therapeutic potential.
Miller, K. N., Dasgupta, N., Liu, T., Adams, P. D., & Vizioli, M. G. (2021) · eLife · doi:10.7554/elife.63728 · Cited by 55 · see citing works
The struggle of a good friend getting old: cellular senescence in viral responses and therapy
Kohli, J., Veenstra, I., & Demaria, M. (2021) · The EMBO Reports · doi:10.15252/embr.202052243 · Cited by 52 · see citing works
Luo, W.-W., Tong, Z., Cao, P., Wang, F.-B., Liu, Y., Zheng, Z.-Q., Wang, S.-Y., Li, S., & Wang, Y.-Y. (2022) · Nature Communications · doi:10.1038/s41467-022-32401-1 · Cited by 53 · see citing works
Ligands stimulating antitumour immunity as the next G-quadruplex challenge
Miglietta, G., Marinello, J., Russo, M., & Capranico, G. (2022) · Molecular Cancer · doi:10.1186/s12943-022-01649-y · Cited by 44 · see citing works
The functional impact of nuclear reorganization in cellular senescence
Rocha, A., Dalgarno, A., & Neretti, N. (2022) · Briefings in Functional Genomics · doi:10.1093/bfgp/elab012 · Cited by 38 · see citing works
He, S., Li, X., Mittra, N., Bhattacharjee, A., Wang, H., Song, S., Zhao, S., Liu, F., & Han, X. (2025) · Advanced Science · doi:10.1002/advs.202410910 · Cited by 34 · see citing works
Self-citationNuclear envelope disruption triggers hallmarks of aging in lung alveolar macrophages
De Silva, N. S., Siewiera, J., Alkhoury, C., Nader, G. P. F., Nadalin, F., de Azevedo, K., Couty, M., Izquierdo, H. M., Bhargava, A., Conrad, C., et al. (2023) · Nature Aging · doi:10.1038/s43587-023-00488-w · Cited by 34 · see citing works
Mitochondrial epigenetics regulating inflammation in cancer and aging
Chatterjee, D., Das, P., & Chakrabarti, O. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.929708 · Cited by 33 · see citing works
Unraveling Adipocytes and Cancer Links: Is There a Role for Senescence?
Wu, Q., Li, B., Sun, S., & Sun, S. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.00282 · Cited by 24 · see citing works
Alshebremi, M., Tomchuck, S. L., Myers, J. T., Kingsley, D. T., Eid, S., Abiff, M., Bonner, M., Saab, S. T., Choi, S. H., & Huang, A. Y.-C. (2023) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2022-006608 · Cited by 14 · see citing works
“Detection of cytosolic dsDNA in the context of viral and bacterial infections, 26–29 aging and damaged cells, 30 or cancer, 31–33 is performed by the cytoplasmic DNA sensor, cGAS. cGAS catalyzes the formation of the second messenger cyclic dinucleotide (CDN), 2 ′ 3 ′ -cyclic- GMP-AMP (cGAMP).”
Pericentromeric repetitive ncRNA regulates chromatin interaction and inflammatory gene expression
Miyata, K., & Takahashi, A. (2022) · Nucleus · doi:10.1080/19491034.2022.2034269 · Cited by 5 · see citing works
- Authors
- Yang, H., Wang, H., Ren, J., Chen, Q., & Chen, Z. J.
- Affiliations
- The University of Texas Southwestern Medical Center (US)
- Fujian Normal University (CN)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Chen, Zhijian J.
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2017-05-22
- Volume
- 114
- Issue
- 23
- Pages
- E4612-E4620
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC5468617
- OpenAlex
- W2618634776
- Semantic Scholar
- 53932ad7980bdead587fef743782fa6dea315c0c
- Cited by
- 1,009
- References
- 54
- Citations by year
- 2026: 90 · 2025: 109 · 2024: 130 · 2023: 127 · 2022: 125 · 2021: 119 · 2020: 125 · 2019: 96 · 2018: 66 · 2017: 22
- FWCI
- 62.55
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute (HHMI)
- Cancer Prevention and Research Institute of Texas (RP120718, RP150498)
- Welch Foundation (I-1389)
- Fujian Normal University (FJNU)
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- cGAS, cellular senescence, DNA damage response, senescence-associated secretory phenotype, cytosolic DNA sensors, innate immunity, cell immortalization, mouse embryonic fibroblasts, radiation-induced DNA damage, etoposide, cGAMP, lung adenocarcinoma, survival prediction, antitumor immunity
- MeSH terms
- Mouse Embryonic Stem Cells, Adenocarcinoma of Lung, Cyclic Guanosine Monophosphate-Adenosine Monophosphate Synthase, Adenocarcinoma, Animals, Cells, Cultured, Cytosol, DNA Damage, Fibroblasts, Humans, Immunity, Innate, Lung Neoplasms, Nucleotidyltransferases, Phenotype, Prognosis, Gene Expression, Cellular Senescence, Mice, Knockout, Mice, HEK293 Cells
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