The DOI matches its Crossref record; 37 of the 37 references it cites were found in a registry or an index.
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“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]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“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]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“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]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“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]
The cited source says what the claim attributes to it.
In the citing paper
“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]
The cited source says what the claim attributes to it.
In the citing paper
“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 cited source says what the claim attributes to it.
In the citing paper
“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
The cited source says what the claim attributes to it.
In the citing paper
“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]
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“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]
Experimental — accuracy not yet measuredIn the citing paper
“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
In the citing paper
“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
In the citing paper
“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
In the citing paper
“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]
In the citing paper
“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
In the citing paper
“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
In the citing paper
“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 the citing paper
“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
In the citing paper
“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
In the citing paper
“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]
In the citing paper
“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]
In the citing paper
“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]
In the citing paper
“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]
In the citing paper
“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]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
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
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
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
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×
“, 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
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
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 2,628
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
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
Debacq-Chainiaux, F., Erusalimsky, J. D., Campisi, J., & Toussaint, O. (2009) · Nature Protocols · doi:10.1038/nprot.2009.191 · Cited by 1,668
Flagged first, then by citations
Cited by
Sorted by citations
Items 401–500 of 1,001
Novel insight into cGAS-STING pathway in ischemic stroke: from pre- to post-disease
Ma, X., Xin, D., She, R., Liu, D., Ge, J., & Mei, Z. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1275408 · Cited by 52
Regulation and inhibition of the DNA sensor cGAS
Hertzog, J., & Rehwinkel, J. (2020) · EMBO Reports · doi:10.15252/embr.202051345 · Cited by 52
Biological functions and theranostic potential of HMGB family members in human cancers
Niu, L., Yang, W., Duan, L., Wang, X., Li, Y., Xu, C., Liu, C., Zhang, Y., Zhou, W. J., Liu, J., et al. (2020) · Therapeutic Advances in Medical Oncology · doi:10.1177/1758835920970850 · Cited by 51
Self-citationcGAS‐STING pathway: post‐translational modifications and functions in sterile inflammatory diseases
Hong, Z., Ma, T., Liu, X., & Wang, C. (2021) · FEBS Journal · doi:10.1111/febs.16137 · Cited by 52
Control of innate immunity by the cGAS‐STING pathway
Mosallanejad, K., & Kagan, J. C. (2022) · Immunology and Cell Biology · doi:10.1111/imcb.12555 · Cited by 52
The cGAS-STING pathway: a therapeutic target in diabetes and its complications
He, W., Mu, X., Wu, X., Liu, Y., Deng, J., Liu, Y., Han, F. Y., & Nie, X. (2023) · Burns & Trauma · doi:10.1093/burnst/tkad050 · Cited by 50
Microglia-derived extracellular vesicles trigger age-related neurodegeneration upon DNA damage
Arvanitaki, E. S., Goulielmaki, E., Gkirtzimanaki, K., Niotis, G., Tsakani, E., Nenedaki, E., Rouska, I., Kefalogianni, M., Xydias, D., Kalafatakis, I., et al. (2024) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2317402121 · Cited by 50
Endogenous Nucleic Acid Recognition by RIG-I-Like Receptors and cGAS
Lee, J., Chiang, C., & Gack, M. U. (2019) · Journal of Interferon & Cytokine Research · doi:10.1089/jir.2019.0015 · Cited by 50
The aging proteostasis decline: From nematode to human
Meller, A., & Shalgi, R. (2021) · Experimental Cell Research · doi:10.1016/j.yexcr.2021.112474 · Cited by 51
cGAS/STING: novel perspectives of the classic pathway
Gao, M., He, Y., Tang, H., Chen, X., Liu, S., & Tao, Y. (2020) · Molecular Biomedicine · doi:10.1186/s43556-020-00006-z · Cited by 50
Aging, Senescence, and Dementia
Behfar, Q., Zuniga, A. R., & Adami, P. V. M. (2022) · The Journal of Prevention of Alzheimer s Disease · doi:10.14283/jpad.2022.42 · Cited by 52
Updated roles of cGAS-STING signaling in autoimmune diseases
Liu, Y., & Pu, F. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1254915 · Cited by 50
Du, M., Sun, L., Guo, J. J., & Lv, H. (2024) · Pharmacological Research · doi:10.1016/j.phrs.2024.107198 · Cited by 51
Biomarkers of ageing of humans and non-human primates
Wu, Z., Qu, J. T., Zhang, W., Bao, Z., Bi, Y., Cai, J.-P., Cai, S.-Q., Cao, C.-M., Cao, F., Cao, Z., et al. (2025) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-025-00883-8 · Cited by 52
Sharma, P., Barlow, W. E., Godwin, A. K., Parkes, E. E., Knight, L. A., Walker, S. M., Kennedy, R. D., Harkin, D. P., Logan, G. E., Steele, C., et al. (2019) · Journal of Clinical Oncology · doi:10.1200/jco.19.00693 · Cited by 49
Cancer Response to Therapy-Induced Senescence: A Matter of Dose and Timing
Mongiardi, M. P., Pellegrini, M., Pallini, R., Levi, A., & Falchetti, M. L. (2021) · Cancers · doi:10.3390/cancers13030484 · Cited by 49
Santa, P., Garreau, A., Serpas, L., Ferrière, A., Blanco, P., Soni, C., & Sisirak, V. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.629922 · Cited by 56
Liang, C., Ke, Q., Liu, Z., Ren, J., Zhang, W., Hu, J., Wang, Z., Chen, H., Xia, K., Lai, X., et al. (2022) · Nucleic Acids Research · doi:10.1093/nar/gkac146 · Cited by 50
Aging-associated accumulation of mitochondrial DNA mutations in tumor origin
Kong, M., Guo, L., Xu, W., He, C., Jia, X., Zhao, Z., & Gu, Z. (2022) · Life Medicine · doi:10.1093/lifemedi/lnac014 · Cited by 51
Wu, L., Zhang, Z., Bai, M., Yan, Y., Yu, J., & Xu, Y. (2023) · Cell Communication and Signaling · doi:10.1186/s12964-023-01139-8 · Cited by 48
Zhen, Z., Chen, Y., Wang, H., Tang, H., Zhang, H., Liu, H., Jiang, Y., & Mao, Z. (2023) · Nature Communications · doi:10.1038/s41467-023-43001-y · Cited by 52
Senolytic therapeutics: An emerging treatment modality for osteoarthritis
Ansari, M. M., Ghosh, M., Lee, D., & Son, Y. (2024) · Ageing Research Reviews · doi:10.1016/j.arr.2024.102275 · Cited by 49
STING signals to NF-κB from late endolysosomal compartments using IRF3 as an adaptor
Zhang, B., Pedersen, A., Reinert, L. S., Li, Y., Narita, R., Idorn, M., Hu, L., Skouboe, M. K., Li, S., Maimaitili, M., et al. (2025) · Nature Immunology · doi:10.1038/s41590-025-02283-8 · Cited by 49
NF‐κB/IKK activation by small extracellular vesicles within the SASP
Fafián‐Labora, J., & O’Loghlen, A. (2021) · Aging Cell · doi:10.1111/acel.13426 · Cited by 49
Gong, W., Liu, P., Zhao, F., Liu, J., Hong, Z., Ren, H., Gu, G., Wang, G., Wu, X., Zheng, T., et al. (2021) · Inflammatory Bowel Diseases · doi:10.1093/ibd/izab217 · Cited by 48
Mechanotransduction in response to ECM stiffening impairs cGAS immune signaling in tumor cells
Liu, Y., Yao, X., Zhao, Y., Fang, D., Shi, L., Yang, L., Song, G., Cai, K., Li, L., Deng, Q., et al. (2023) · Cell Reports · doi:10.1016/j.celrep.2023.113213 · Cited by 48
Xu, H., Wedn, A. M., Wang, J., Gu, Y., Liu, H., Zhang, J., Lin, Z., Zhou, R., Pang, X., & Cui, Y. (2024) · Pharmacological Research · doi:10.1016/j.phrs.2024.107063 · Cited by 49
Wang, K., Cao, Q., Liu, L., Zhao, Z.-J., Liu, W., Zhou, D., Tan, C.-P., Xia, W. T., Ji, L., & Mao, Z. (2019) · Chemical Science · doi:10.1039/c9sc03594j · Cited by 47
The hallmarks of aging in Ataxia-Telangiectasia
Aguado, J., Gómez‐Inclán, C., Leeson, H. C., Lavin, M. F., Shiloh, Y., & Wolvetang, E. J. (2022) · Ageing Research Reviews · doi:10.1016/j.arr.2022.101653 · Cited by 47
Non-lethal outcomes of engaging regulated cell death pathways in cancer
Kalkavan, H., Rühl, S., Shaw, J. J. P., & Green, D. R. (2023) · Nature Cancer · doi:10.1038/s43018-023-00571-6 · Cited by 48
Song, M. J., Park, C., Kim, H., Han, S., Lee, S., Lee, D. H., & Chung, J. H. (2023) · Aging Cell · doi:10.1111/acel.14000 · Cited by 47
Recent Advances in Aging and Immunosenescence: Mechanisms and Therapeutic Strategies
Wang, S., Huo, T., Lu, M., Zhao, Y., Zhang, J., He, W., & Chen, H. (2025) · Cells · doi:10.3390/cells14070499 · Cited by 47
Oxidative stress-induced senescence markedly increases disc cell bioenergetics
Patil, P. R., Falabella, M., Saeed, A., Lee, D., Kaufman, B. A., Shiva, S., Croix, C. M. S., Houten, B. V., Niedernhofer, L. J., Robbins, P. D., et al. (2019) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2019.04.006 · Cited by 46
The triggers of the cGAS-STING pathway and the connection with inflammatory and autoimmune diseases
Zhou, R., Xie, X., Li, X., Qin, Z., Wei, C., Liu, J., & Luo, Y. (2019) · Infection Genetics and Evolution · doi:10.1016/j.meegid.2019.104094 · Cited by 46
Chen, C., Yang, R., & Xu, H. (2021) · Journal of Gastroenterology · doi:10.1007/s00535-021-01803-1 · Cited by 48
Microglial cGAS–STING signaling underlies glaucoma pathogenesis
Liu, Y., Wang, A., Chen, C., Zhang, Q., Shen, Q., Zhang, D., Xiao, X., Chen, S., Lian, L., Le, Z., et al. (2024) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2409493121 · Cited by 47
Role of Post-Translational Modifications of cGAS in Innate Immunity
Wu, Y., & Li, S. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21217842 · Cited by 47
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
“In addition, it has to be considered that high expression levels of STING can exhibit a strong NF-kB signature that can drive tumorigenesis through chronic inflammation [137].”
BackgroundDNA hypomethylation leads to cGAS‐induced autoinflammation in the epidermis
Beck, M. A., Fischer, H., Grabner, L., Groffics, T., Winter, M., Tangermann, S., Meischel, T., Zaussinger‐Haas, B., Wagner, P., Fischer, C., et al. (2021) · The EMBO Journal · doi:10.15252/embj.2021108234 · Cited by 44
Regulation and function of the cGAS-MITA/STING axis in health and disease
Zhang, Z.-D., & Zhong, B. (2022) · Cell Insight · doi:10.1016/j.cellin.2021.100001 · Cited by 44
Zheng, L., He, S., Wang, H., Li, J., Liu, Y., & Liu, S. (2024) · Aging and Disease · doi:10.14336/ad.2024.0206 · Cited by 46
Genomic instability as a driver and suppressor of anti-tumor immunity
Requesens, M., Foijer, F., Nijman, H. W., & de Bruyn, M. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1462496 · Cited by 45
Mitochondrial dysfunction in cellular senescence: a bridge to neurodegenerative disease
Hruby, A. J., & Higuchi‐Sanabria, R. (2025) · npj Aging · doi:10.1038/s41514-025-00291-4 · Cited by 52
A tale of the good and bad: Cell senescence in bone homeostasis and disease
Liu, X., & Wan, M. (2019) · International review of cytology · doi:10.1016/bs.ircmb.2019.03.005 · Cited by 45
Pathophysiological Role of Organelle Stress/Crosstalk in AKI-to-CKD Transition
Maekawa, H., & Inagi, R. (2019) · Seminars in Nephrology · doi:10.1016/j.semnephrol.2019.10.007 · Cited by 45
Nuclear deformations, from signaling to perturbation and damage
Nader, G. P. F., Williart, A., & Piel, M. (2021) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2021.07.008 · Cited by 49
Medicinal chemistry perspective on cGAS-STING signaling pathway with small molecule inhibitors
Tian, X., Xu, F., Zhu, Q., Feng, Z., Dai, W., Zhou, Y.-L., You, Q., & Xu, X. (2022) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2022.114791 · Cited by 44
STING SNP R293Q Is Associated with a Decreased Risk of Aging-Related Diseases
Hamann, L., Ruiz-Moreno, J. S., Szwed, M., Mossakowska, M., Lundvall, L., Schumann, R. R., Opitz, B., & Puzianowska-Kuznicka, M. (2019) · Gerontology · doi:10.1159/000492972 · Cited by 43
Genomic instability and innate immune responses to self-DNA in progeria
Gonzalo, S., & Coll-Bonfill, N. (2019) · GeroScience · doi:10.1007/s11357-019-00082-2 · Cited by 44
Man, C. H., Lam, W., Dang, C. C., Zeng, X.-Y., Zheng, L., Chan, N. N.-M., Ng, K.-L., Chan, K.-C., Kwok, T.-H., Ng, T. C.-C., et al. (2023) · Blood · doi:10.1182/blood.2023019782 · Cited by 44
Self-citationDeregulated transcription factors in the emerging cancer hallmarks
Hasan, A., Khan, N. A., Shahab Uddin, M. S., Khan, A. Q., & Steinhoff, M. S. (2023) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2023.12.001 · Cited by 45
Li, H., Zhang, C., Chen, Y., Xu, Y., Yao, W., & Fan, W. (2024) · ACS Nano · doi:10.1021/acsnano.4c08463 · Cited by 43
Trussoni, C. E., O’Hara, S. P., & LaRusso, N. F. (2022) · Seminars in Immunopathology · doi:10.1007/s00281-022-00909-9 · Cited by 44
Li, X., Li, X., Xie, C., Cai, S., Li, M., Jin, H., Wu, S., Cui, J., Liu, H., & Zhao, Y. B. (2021) · Protein & Cell · doi:10.1007/s13238-021-00879-y · Cited by 44
Frediani, E., Scavone, F., Laurenzana, A., Chillà, A., Tortora, K., Cimmino, I., Leri, M., Bucciantini, M., Mangoni, M., Fibbi, G., et al. (2022) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.17255 · Cited by 43
STING mediates nuclear PD-L1 targeting-induced senescence in cancer cells
Lee, J., Kim, S. Y., Kim, S. H., Choi, S., Lee, B., & Shin, J. (2022) · Cell Death and Disease · doi:10.1038/s41419-022-05217-6 · Cited by 43
Beyond DNA sensing: expanding the role of cGAS/STING in immunity and diseases
Seok, J. K., Kim, M., Kang, H. C., Cho, Y., Lee, H. S., & Lee, J. Y. (2023) · Archives of Pharmacal Research · doi:10.1007/s12272-023-01452-3 · Cited by 45
ATM-deficiency-induced microglial activation promotes neurodegeneration in ataxia-telangiectasia
Lai, J. F., Demirbas, D., Kim, J., Jeffries, A. M., Tolles, A. K., Park, J., Chittenden, T. W., Buckley, P. G., Yu, T. W., Lodato, M. A., et al. (2023) · Cell Reports · doi:10.1016/j.celrep.2023.113622 · Cited by 46
Xue, H., Zhao, B., Towers, M., Liao, L., Luzete-Monteiro, E., Xu, X., Freeman, C., Peng, H., Tang, H., Havas, A. P., et al. (2024) · Nature Aging · doi:10.1038/s43587-023-00564-1 · Cited by 44
Self-citationRecent advances in senescence-associated secretory phenotype and osteoporosis
Fan, H., Qiao, Z., Li, J., Shang, G., Shang, C., Chen, S., Leng, Z., Su, H., Kou, H., & Liu, H. (2024) · Heliyon · doi:10.1016/j.heliyon.2024.e25538 · Cited by 42
Cellular senescence in liver diseases: From molecular drivers to therapeutic targeting
Du, K., Umbaugh, D. S., Ren, N., & Diehl, A. M. (2025) · Journal of Hepatology · doi:10.1016/j.jhep.2025.08.021 · Cited by 42
Inflammatory signaling in genomically instable cancers
Talens, F., & van Vugt, M. A. T. M. (2019) · Cell Cycle · doi:10.1080/15384101.2019.1638192 · Cited by 43
Cellular senescence: from anti-cancer weapon to anti-aging target
Yuan, L., Alexander, P. B., & Wang, X. (2020) · Science China Life Sciences · doi:10.1007/s11427-019-1629-6 · Cited by 42
HMGB1 orchestrates STING-mediated senescence via TRIM30α modulation in cancer cells
Lee, J., Park, I. H., Kwak, M. S., Rhee, W. J., Kim, S. H., & Shin, J. (2021) · Cell Death Discovery · doi:10.1038/s41420-021-00409-z · Cited by 42
cGAS-STING Signaling Pathway and Liver Disease: From Basic Research to Clinical Practice
Chen, B., Rao, X., Wang, X., Luo, Z., Wang, J., Sheng, S., Liu, Y., Zhang, N., Jin, S., Chen, H., et al. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.719644 · Cited by 42
Senescent cells at the crossroads of aging, disease, and tissue homeostasis
Kuehnemann, C., & Wiley, C. D. (2023) · Aging Cell · doi:10.1111/acel.13988 · Cited by 44
Colangelo, N. W., Gerber, N. K., Vatner, R. E., & Cooper, B. T. (2024) · Frontiers in Pharmacology · doi:10.3389/fphar.2024.1383000 · Cited by 44
Miller, K. N., Li, B., Pierce-Hoffman, H. R., Patel, S., Lei, X., Rajesh, A., Teneche, M. G., Havas, A. P., Gandhi, A., Macip, C. C., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-57229-3 · Cited by 47
Self-citationImpact of cancer evolution on immune surveillance and checkpoint inhibitor response
Wu, Y., Biswas, D., & Swanton, C. (2021) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2021.02.013 · Cited by 43
Epigenetic Underpinnings of Inflammation: A Key to Unlock the Tumor Microenvironment in Glioblastoma
Chen, N., Peng, C. Y., & Li, D. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.869307 · Cited by 43
Cellular senescence and neurodegeneration
Holloway, K., Neherin, K., Dam, K. U., & Zhang, H. (2023) · Human Genetics · doi:10.1007/s00439-023-02565-x · Cited by 40
Telomeres as hotspots for innate immunity and inflammation
Nassour, J., Przetocka, S., & Karlseder, J. (2023) · DNA repair · doi:10.1016/j.dnarep.2023.103591 · Cited by 40
Inflammation and mitophagy are mitochondrial checkpoints to aging
Guilbaud, E., Sarosiek, K. A., & Galluzzi, L. (2024) · Nature Communications · doi:10.1038/s41467-024-47840-1 · Cited by 42
Targeting chromosomal instability in patients with cancer
Al-Rawi, D. H., Lettera, E., Li, J., Bona, M. D., & Bakhoum, S. F. W. (2024) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-024-00923-w · Cited by 41
The extent of liver injury determines hepatocyte fate toward senescence or cancer
Wang, C., Chen, W., Wu, Y., You, P., Zheng, S., Liu, C.-C., Xiang, D., Wang, M., Cai, Y., Zhao, Q., et al. (2018) · Cell Death and Disease · doi:10.1038/s41419-018-0622-x · Cited by 40
Self-citationLei, Z., Tang, Q., Ju, Y., Lin, Y., Bai, X., Luo, H., & Tong, Z. (2020) · Journal of Biomaterials Science Polymer Edition · doi:10.1080/09205063.2020.1713451 · Cited by 40
Self-citationRadiation induces primary osteocyte senescence phenotype and affects osteoclastogenesis in vitro
Wang, Y., Xu, L., Wang, J., Bai, J., Zhai, J., & Zhu, G. (2021) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2021.4909 · Cited by 41
Human Hair Graying Revisited: Principles, Misconceptions, and Key Research Frontiers
Paus, R., Sevilla, A., & Grichnik, J. M. (2023) · Journal of Investigative Dermatology · doi:10.1016/j.jid.2023.09.276 · Cited by 39
Nucleic Acid Immunity and DNA Damage Response: New Friends and Old Foes
Taffoni, C., Steer, A., Marines, J., Chamma, H., Vila, I. K., & Laguette, N. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.660560 · Cited by 39
Old and New Players of Inflammation and Their Relationship With Cancer Development
Chavez-Dominguez, R., Perez-Medina, M., Aguilar‐Cázares, D., Galicia-Velasco, M., Meneses-Flores, M., Islas-Vázquez, L., Camarena, Á., & López-González, J. S. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.722999 · Cited by 40
Senescence of Tumor Cells in Anticancer Therapy—Beneficial and Detrimental Effects
Piskorz, W. M., & Cechowska‐Pasko, M. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms231911082 · Cited by 39
Uceda-Castro, R., Margarido, A. S., Cornet, L., Vegna, S., Hahn, K., Song, J., Putavet, D. A., van Geldorp, M., Çitirikkaya, C. H., de Keizer, P. L. J., et al. (2022) · Cell Reports Medicine · doi:10.1016/j.xcrm.2022.100821 · Cited by 40
The Role of cGAS-STING in Age-Related Diseases from Mechanisms to Therapies
Zheng, W., Feng, D., Xiong, X., Liao, X., Wang, S., Xu, H., Le, W., Wei, Q., & Yang, L. (2023) · Aging and Disease · doi:10.14336/ad.2023.0117 · Cited by 39
Autophagy Governs Protumorigenic Effects of Mitotic Slippage–induced Senescence
Jakhar, R., Luijten, M., Wong, A. X. F., Cheng, B., Guo, K., Neo, S. P., Au, B. V., Kulkarni, M., Lim, K. J., Maimaiti, J., et al. (2018) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-18-0024 · Cited by 39
Behind the Wheel of Epithelial Plasticity in KRAS-Driven Cancers
Arner, E. N., Du, W., & Brekken, R. A. (2019) · Frontiers in Oncology · doi:10.3389/fonc.2019.01049 · Cited by 40
Alerting the immune system to DNA damage: micronuclei as mediators
MacDonald, K. M., Benguerfi, S., & Harding, S. M. (2020) · Essays in Biochemistry · doi:10.1042/ebc20200016 · Cited by 39
Cellular Senescence Variation by Metabolic and Epigenomic Remodeling
Nakao, M., Tanaka, H., & Koga, T. (2020) · Trends in Cell Biology · doi:10.1016/j.tcb.2020.08.009 · Cited by 39
Metabolic Alterations in Cellular Senescence: The Role of Citrate in Ageing and Age-Related Disease
Mycielska, M. E., James, E. N., & Parkinson, E. K. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23073652 · Cited by 38
Ren, C., Jin, J., Li, C., Xiang, J., Wu, Y., Zhou, Y., Sun, L., Zhang, X., & Tian, N. (2022) · Journal of Cell Science · doi:10.1242/jcs.259738 · Cited by 38
Ferritin in cancer therapy: A pleiotropic tumoraffin nanocage‐based transport
Deng, G., Li, Y., Liang, N., Hu, P., Zhang, Y., Qiao, L., Zhang, Y., Xie, J., Luo, H., Wang, F., et al. (2023) · Cancer Medicine · doi:10.1002/cam4.5778 · Cited by 38
Deb, V. K., & Jain, U. (2024) · Drug Delivery and Translational Research · doi:10.1007/s13346-024-01572-3 · Cited by 37
Mechanism and role of nuclear laminin B1 in cell senescence and malignant tumors
Lv, T., Wang, C., Zhou, J., Feng, X., Zhang, L., & Fan, Z. (2024) · Cell Death Discovery · doi:10.1038/s41420-024-02045-9 · Cited by 38
Changes in the biochemical taste of cytoplasmic and cell-free DNA are major fuels for inflamm-aging
Storci, G., Carolis, S. D., Olivieri, F., & Bonafè, M. (2018) · Seminars in Immunology · doi:10.1016/j.smim.2018.08.003 · Cited by 37
Mechanistic link between DNA damage sensing, repairing and signaling factors and immune signaling
Mukherjee, S., Abdisalaam, S., Bhattacharya, S., Kalayarasan, S., Sinha, D., & Asaithamby, A. (2019) · Advances in protein chemistry and structural biology · doi:10.1016/bs.apcsb.2018.11.004 · Cited by 39
miR-23a/b suppress cGAS-mediated innate and autoimmunity
Yu, Q., Chu, L., Li, Y., Wang, Q., Zhu, J., Wang, C., & Cui, S. (2021) · Cellular & Molecular Immunology · doi:10.1038/s41423-021-00668-x · Cited by 37
Self-citationEZH2–CCF–cGAS Axis Promotes Breast Cancer Metastasis
Duan, D., Shang, M., Han, Y., Liu, J., Liu, J., Kong, S. H., Hou, J., Huang, B., Lü, J., & Zhang, Y. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23031788 · Cited by 37
Das, U. N. (2022) · European Journal of Clinical Nutrition · doi:10.1038/s41430-022-01173-8 · Cited by 37
Intervention of cGAS‒STING signaling in sterile inflammatory diseases
Hong, Z., Mei, J., Guo, H., Zhu, J., & Wang, C. (2022) · Journal of Molecular Cell Biology · doi:10.1093/jmcb/mjac005 · Cited by 38
Self-citationDNA damage response(DDR): a link between cellular senescence and human cytomegalovirus
Wu, X., Zhou, X., Wang, S., & Mao, G. (2023) · Virology Journal · doi:10.1186/s12985-023-02203-y · Cited by 41
Ferroptosis Inducers as Promising Radiosensitizer Agents in Cancer Radiotherapy
Jalali-Zefrei, F., Shormij, M., Dastranj, L., Alvandi, M., Shaghaghi, Z., Farzipour, S., & Polgardani, N. Z. (2023) · Current Radiopharmaceuticals · doi:10.2174/0118744710262369231110065230 · Cited by 39
Metadata
- 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
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
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 ›
Are you an author, or do you see a problem with this page? Request a review
