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
Cited by
Sorted by citations
Items 101–200 of 1,001
Jiang, H., Xue, X., Panda, S., Kawale, A. S., Hooy, R. M., Liang, F., Sohn, J., Sung, P., & Gekara, N. O. (2019) · The EMBO Journal · doi:10.15252/embj.2019102718 · Cited by 270
Bird, T. G., Müller, M., Boulter, L., Vincent, D. F., Ridgway, R. A., Lopez-Guadamillas, E., Lu, W.-Y., Jamieson, T., Govaere, O., Campbell, A. D., et al. (2018) · Science Translational Medicine · doi:10.1126/scitranslmed.aan1230 · Cited by 261
Guo, Q., Chen, X., Chen, J., Zheng, G., Xie, C., Wu, H., Miao, Z., Lin, Y., Wang, X., Gao, W., et al. (2021) · Cell Death and Disease · doi:10.1038/s41419-020-03341-9 · Cited by 261
Self-citationDu, S.-S., Chen, G.-W., Yang, P., Chen, Y.-X., Hu, Y., Zhao, Q.-Q., Zhang, Y., Liu, R., Zheng, D.-X., Zhou, J., et al. (2022) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/j.ijrobp.2021.12.162 · Cited by 267
Structural basis for sequestration and autoinhibition of cGAS by chromatin
Michalski, S., de Oliveira Mann, C. C., Stafford, C. A., Witte, G., Bartho, J., Lammens, K., Hornung, V., & Hopfner, K.-P. (2020) · Nature · doi:10.1038/s41586-020-2748-0 · Cited by 256
Hu, X., Zhang, H., Zhang, Q., Yao, X. X., Ni, W., & Zhou, K. (2022) · Journal of Neuroinflammation · doi:10.1186/s12974-022-02602-y · Cited by 271
cGAS/STING axis mediates a topoisomerase II inhibitor–induced tumor immunogenicity
Wang, Z., Chen, J., Hu, J., Zhang, H., Xu, F., He, W., Wang, X., Li, M., Lu, W., Zeng, G., et al. (2019) · Journal of Clinical Investigation · doi:10.1172/jci127471 · Cited by 253
STING inhibits the reactivation of dormant metastasis in lung adenocarcinoma
Hu, J. Y., Rivera, F. J. S., Wang, Z., Johnson, G. N., Ho, Y.-J., Ganesh, K., Umeda, S., Gan, S., Mujal, A. M., Delconte, R. B., et al. (2023) · Nature · doi:10.1038/s41586-023-05880-5 · Cited by 261
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
Challenges and Opportunities in the Clinical Development of STING Agonists for Cancer Immunotherapy
Aval, L. M., Pease, J. E., Sharma, R., & Pinato, D. J. (2020) · Journal of Clinical Medicine · doi:10.3390/jcm9103323 · Cited by 253
Gentili, M., Lahaye, X., Nadalin, F., Nader, G. P. F., Lombardi, E. P., Hervé, S., Silva, N. S. D., Rookhuizen, D. C., Zueva, E., Goudot, C., et al. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.01.105 · Cited by 256
Mitochondrial DNA-triggered innate immune response: mechanisms and diseases
Hu, M.-M., & Shu, H. (2023) · Cellular and Molecular Immunology · doi:10.1038/s41423-023-01086-x · Cited by 263
The cGAS-cGAMP-STING Pathway: A Molecular Link Between Immunity and Metabolism
Bai, J., & Liu, F. (2019) · Diabetes · doi:10.2337/dbi18-0052 · Cited by 253
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
Phosphorylation and chromatin tethering prevent cGAS activation during mitosis
Li, T., Huang, T., Du, M., Chen, X., Du, F., Ren, J., & Chen, Z. J. (2021) · Science · doi:10.1126/science.abc5386 · Cited by 247
Senolytic therapies for healthy longevity.
van Deursen, J. M. (2019) · Science · doi:10.1126/science.aaw1299 · Cited by 237
Cellular senescence at the crossroads of inflammation and Alzheimer's disease
Guerrero, A., De Strooper, B., & Arancibia-Cárcamo, I. L. (2021) · Trends in Neurosciences · doi:10.1016/j.tins.2021.06.007 · Cited by 236
The Impact of Radiation-Induced DNA Damage on cGAS-STING-Mediated Immune Responses to Cancer
Storozynsky, Q. T., & Hitt, M. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21228877 · Cited by 236
Loo, T. M., Miyata, K., Tanaka, Y., & Takahashi, A. (2020) · Cancer Science · doi:10.1111/cas.14266 · Cited by 232
Classical and Nonclassical Intercellular Communication in Senescence and Ageing
Fafián‐Labora, J., & O’Loghlen, A. (2020) · Trends in Cell Biology · doi:10.1016/j.tcb.2020.05.003 · Cited by 244
Two-Step Senescence-Focused Cancer Therapies
Sieben, C. J., Sturmlechner, I., van de Sluis, B., & van Deursen, J. M. (2018) · Trends in Cell Biology · doi:10.1016/j.tcb.2018.04.006 · Cited by 222
Upadhyay, N., Upadhyay, S., Abed, S. S., & Dwivedi, Y. K. (2022) · International Journal of Bank Marketing · doi:10.1108/ijbm-06-2021-0262 · Cited by 157
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
Emerging roles of extracellular vesicles in cellular senescence and aging
Takasugi, M. (2018) · Aging Cell · doi:10.1111/acel.12734 · Cited by 227
Zhang, Z., Zhou, H., Ouyang, X., Dong, Y., Sarapultsev, A., Luo, S., & Hu, D. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01252-z · Cited by 222
Zhang, M., Yang, W. Z., Wang, P., Deng, Y., Dong, Y., Liu, F., Huang, R., Zhang, P., Duan, Y., Liu, X., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-19973-6 · Cited by 214
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
ER-directed TREX1 limits cGAS activation at micronuclei
Mohr, L., Toufektchan, E., von Morgen, P., Chu, K., Kapoor, A. R., & Maciejowski, J. (2021) · Molecular Cell · doi:10.1016/j.molcel.2020.12.037 · Cited by 211
Papatheodoridi, A., Chrysavgis, L., Koutsilieris, M., & Chatzigeorgiou, A. (2019) · Hepatology · doi:10.1002/hep.30834 · Cited by 210
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
Coaching from the sidelines: the nuclear periphery in genome regulation
Buchwalter, A. L., Kaneshiro, J. M., & Hetzer, M. W. (2018) · Nature Reviews Genetics · doi:10.1038/s41576-018-0063-5 · Cited by 213
Senescence as a therapeutic target in cancer and age-related diseases
McHugh, D., Durán, I., & Gil, J. (2025) · Nature Reviews Drug Discovery · doi:10.1038/s41573-024-01074-4 · Cited by 197
Cellular senescence in cancer: from mechanisms to detection
Ou, H., Hoffmann, R. J., González‐López, C., Doherty, G. J., Korkola, J. E., & Muñoz‐Espín, D. (2020) · Molecular Oncology · doi:10.1002/1878-0261.12807 · Cited by 208
Activation of STING by targeting a pocket in the transmembrane domain
Lu, D., Shang, G., Li, J., Lu, Y. D., Bai, X., & Zhang, X. (2022) · Nature · doi:10.1038/s41586-022-04559-7 · Cited by 202
The cGAS‒STING pathway in cancer immunity: mechanisms, challenges, and therapeutic implications
Shen, M., Jiang, X., Qiu, P., Oyang, L., Ren, Z., Wang, J., Peng, M., Zhou, Y., Deng, X., & Liao, Q. (2025) · Journal of Hematology & Oncology · doi:10.1186/s13045-025-01691-5 · Cited by 210
LRRC8A:C/E Heteromeric Channels Are Ubiquitous Transporters of cGAMP
Lahey, L. J., Mardjuki, R. E., Wen, X., Hess, G. T., Ritchie, C., Carozza, J. A., Böhnert, V., Maduke, M. C., Bassik, M. C., & Li, L. (2020) · Molecular Cell · doi:10.1016/j.molcel.2020.10.021 · Cited by 201
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
Opposing Roles of Type I Interferons in Cancer Immunity
Boukhaled, G. M., Harding, S. M., & Brooks, D. G. (2020) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev-pathol-031920-093932 · Cited by 208
Extrinsic Phagocyte-Dependent STING Signaling Dictates the Immunogenicity of Dying Cells
Ahn, J., Xia, T., Rabasa, A., Betancourt, D. M., & Barber, G. N. (2018) · Cancer Cell · doi:10.1016/j.ccell.2018.03.027 · Cited by 194
Self-citationYang, Y., Wu, M., Cao, D., Yang, C., Jin, J., Wu, L., Hong, X., Li, W., Lu, L., Li, J., et al. (2021) · Science Advances · doi:10.1126/sciadv.abf6290 · Cited by 187
Ogrodnik, M., Salmonowicz, H., & Gladyshev, V. N. (2019) · Aging Cell · doi:10.1111/acel.12841 · Cited by 184
Old dogs, new trick: classic cancer therapies activate cGAS
Yum, S., Li, M., & Chen, Z. J. (2020) · Cell Research · doi:10.1038/s41422-020-0346-1 · Cited by 184
Liu, P., Li, F., Lin, J., Fukumoto, T., Nacarelli, T., Hao, X., Kossenkov, A. V., Simon, M. C., & Zhang, R. (2021) · Nature Cell Biology · doi:10.1038/s41556-021-00656-3 · Cited by 185
Hepatic stellate cell senescence in liver fibrosis: Characteristics, mechanisms and perspectives
Zhang, M., Salas, S. S., Damba, T., Borghesan, M., Demaria, M., & Moshage, H. J. (2021) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2021.111572 · Cited by 192
Teissier, T., & Boulanger, É. (2019) · Biogerontology · doi:10.1007/s10522-019-09808-3 · Cited by 187
Lai, P., Liu, L., Bancaro, N., Troiani, M., Calì, B., Li, Y., Chen, J., Singh, P. K., Arzola, R. A., Attanasio, G., et al. (2025) · Immunity · doi:10.1016/j.immuni.2025.03.005 · Cited by 174
Yamagishi, R., Kamachi, F., Nakamura, M., Yamazaki, S., Kamiya, T., Takasugi, M., Cheng, Y., Nonaka, Y., Yukawa-Muto, Y., Thuy, L. T. T., et al. (2022) · Science Immunology · doi:10.1126/sciimmunol.abl7209 · Cited by 173
The balance of STING signaling orchestrates immunity in cancer
Lanng, K. R. B., Lauridsen, E. L., & Jakobsen, M. R. (2024) · Nature Immunology · doi:10.1038/s41590-024-01872-3 · Cited by 179
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
Genomic instability, inflammatory signaling and response to cancer immunotherapy
Chen, M., Linstra, R., & van Vugt, M. A. T. M. (2022) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2021.188661 · Cited by 166
Nuclear Membrane Rupture and Its Consequences
Maciejowski, J., & Hatch, E. M. (2020) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-020520-120627 · Cited by 170
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
Histone Acetyltransferase p300 Induces De Novo Super-Enhancers to Drive Cellular Senescence
Sen, P., Lan, Y., Li, C. Y., Sidoli, S., Donahue, G., Dou, Z., Frederick, B., Chen, Q., Luense, L. J., Garcia, B. A., et al. (2019) · Molecular Cell · doi:10.1016/j.molcel.2019.01.021 · Cited by 164
Self-citationThe 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
Muñoz, D. P., Yannone, S. M., Daemen, A., Sun, Y., Vakar-Lopez, F., Kawahara, M., Freund, A. M., Rodier, F., Wu, J. D., Desprez, P.-Y., et al. (2019) · JCI Insight · doi:10.1172/jci.insight.124716 · Cited by 162
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
Lysosomes in senescence and aging
Tan, J. X., & Finkel, T. (2023) · EMBO Reports · doi:10.15252/embr.202357265 · Cited by 178
The innate immune sensor Toll-like receptor 2 controls the senescence-associated secretory phenotype
Hari, P., Millar, F. R., Tarrats, N., Birch, J., Quintanilla, A., Rink, C. J., Fernández-Duran, I., Muir, M., Finch, A. J., Brunton, V. G., et al. (2019) · Science Advances · doi:10.1126/sciadv.aaw0254 · Cited by 154
COVID-19 and cellular senescence
Schmitt, C. A., Tchkonia, T., Niedernhofer, L. J., Robbins, P. D., Kirkland, J. L., & Lee, S. (2023) · Nature Reviews Immunology · doi:10.1038/s41577-022-00785-2 · Cited by 153
Current advances of tubulin inhibitors as dual acting small molecules for cancer therapy
Arnst, K. E., Banerjee, S., Chen, H., Deng, S., Hwang, D., Li, W., & Miller, D. D. (2019) · Medicinal Research Reviews · doi:10.1002/med.21568 · Cited by 156
Tumor cells suppress radiation-induced immunity by hijacking caspase 9 signaling
Han, C., Liu, Z., Zhang, Y., Shen, A., Dong, C., Zhang, A., Moore, C., Ren, Z., Lu, C., Cao, X., et al. (2020) · Nature Immunology · doi:10.1038/s41590-020-0641-5 · Cited by 157
Regulation of the cGAS-STING Pathway
Zhang, B., Xu, P., & Ablasser, A. (2025) · Annual Review of Immunology · doi:10.1146/annurev-immunol-101721-032910 · Cited by 164
The multifaceted role of the SASP in atherosclerosis: from mechanisms to therapeutic opportunities
Sun, Y., Wang, X., Liu, T., Zhu, X., & Pan, X. (2022) · Cell & Bioscience · doi:10.1186/s13578-022-00815-5 · Cited by 156
DNA Replication Stress and Chromosomal Instability: Dangerous Liaisons
Wilhelm, T., Said, M., & Naim, V. (2020) · Genes · doi:10.3390/genes11060642 · Cited by 161
ESCRT-dependent STING degradation inhibits steady-state and cGAMP-induced signalling
Gentili, M., Liu, B., Papanastasiou, M., Dele-Oni, D. O., Schwartz, M. A., Carlson, R. J., Al’Khafaji, A. M., Krug, K., Brown, A., Doench, J. G., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-36132-9 · Cited by 151
Dissecting Aging and Senescence—Current Concepts and Open Lessons
Schmeer, C. W., Kretz, A., Wengerodt, D., Stojiljkovic, M. R., & Witte, O. W. (2019) · Cells · doi:10.3390/cells8111446 · Cited by 156
Hematopoietic aging promotes cancer by fueling IL-1⍺–driven emergency myelopoiesis
Park, M. D., Bérichel, J. L., Hamon, P., Wilk, C. M., Belabed, M., Yatim, N., Saffon, A., Boumelha, J., Falcomatà, C., Tepper, A., et al. (2024) · Science · doi:10.1126/science.adn0327 · Cited by 149
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
Small but mighty: the causes and consequences of micronucleus rupture
Kwon, M., Leibowitz, M. L., & Lee, J. H. (2020) · Experimental & Molecular Medicine · doi:10.1038/s12276-020-00529-z · Cited by 149
Suramin Potently Inhibits cGAMP Synthase, cGAS, in THP1 Cells to Modulate IFN-β Levels
Wang, M., Sooreshjani, M. A., Mikek, C. G., Opoku‐Temeng, C., & Sintim, H. O. (2018) · Future Medicinal Chemistry · doi:10.4155/fmc-2017-0322 · Cited by 144
Li, M., You, L., Xue, J., & Lü, Y. (2018) · Frontiers in Pharmacology · doi:10.3389/fphar.2018.00522 · Cited by 153
Bruand, M., Barras, D., Mina, M., Ghisoni, E., Morotti, M., Lanitis, E., Fahr, N., Desbuisson, M., Grimm, A. J., Zhang, H., et al. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.109412 · Cited by 146
MRE11 liberates cGAS from nucleosome sequestration during tumorigenesis
Cho, M.-G., Kumar, R. J., Lin, C.-C., Boyer, J. A., Shahir, J. A., Fagan‐Solis, K. D., Simpson, D. A., Fan, C., Foster, C. E., Goddard, A. M., et al. (2024) · Nature · doi:10.1038/s41586-023-06889-6 · Cited by 156
Senescent glia link mitochondrial dysfunction and lipid accumulation
Byrns, C. N., Perlegos, A. E., Miller, K. N., Jin, Z., Carranza, F. R., Manchandra, P., Beveridge, C. H., Randolph, C. E., Chaluvadi, V. S., Zhang, S., et al. (2024) · Nature · doi:10.1038/s41586-024-07516-8 · Cited by 147
Self-citationSenescence and the tumor-immune landscape: Implications for cancer immunotherapy
Chibaya, L., Snyder, J. T., & Ruscetti, M. A. (2022) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2022.02.005 · Cited by 146
NAD metabolism: Role in senescence regulation and aging
Chini, C. C. S., Cordeiro, H. S., Tran, N. L. K., & Chini, E. N. (2023) · Aging Cell · doi:10.1111/acel.13920 · Cited by 148
Chemically induced reprogramming to reverse cellular aging
Yang, J.-H., Petty, C. A., Dixon-McDougall, T., Lopez, M. V., Tyshkovskiy, A., Maybury-Lewis, S., Tian, X., Ibrahim, N., Chen, Z., Griffin, P. T., et al. (2023) · Aging · doi:10.18632/aging.204896 · Cited by 136
PARP1 inhibitors trigger innate immunity via PARP1 trapping-induced DNA damage response
Kim, C., Wang, X.-D., & Yu, Y. (2020) · eLife · doi:10.7554/elife.60637 · Cited by 136
Telomeric 8-oxo-guanine drives rapid premature senescence in the absence of telomere shortening
Barnes, R. P., Rosa, M. D., Thosar, S. A., Detwiler, A. C., Roginskaya, V. Y., Houten, B. V., Bruchez, M. P., Stewart-Ornstein, J., & Opresko, P. L. (2022) · Nature Structural & Molecular Biology · doi:10.1038/s41594-022-00790-y · Cited by 142
Role of the inflammation-autophagy-senescence integrative network in osteoarthritis
Vinatier, C., Domínguez, E., Guicheux, J., & Caramés, B. (2018) · Frontiers in Physiology · doi:10.3389/fphys.2018.00706 · Cited by 135
Context-dependent functions of pattern recognition receptors in cancer
Man, S. M., & Jenkins, B. J. (2022) · Nature reviews. Cancer · doi:10.1038/s41568-022-00462-5 · Cited by 143
Chromosomal instability as a driver of cancer progression
Chen, X., Agustinus, A. S., Li, J., Bona, M. D., & Bakhoum, S. F. W. (2024) · Nature Reviews Genetics · doi:10.1038/s41576-024-00761-7 · Cited by 146
The cGAS‐STING pathway: The role of self‐DNA sensing in inflammatory lung disease
Ma, R., Serrano, T. P. O., Davis, J., Prigge, A. D., & Ridge, K. M. (2020) · The FASEB Journal · doi:10.1096/fj.202001607r · Cited by 138
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
Upregulation of PD-L1 in Senescence and Aging
Onorati, A., Havas, A. P., Lin, B., Rajagopal, J., Sen, P., Adams, P. D., & Dou, Z. (2022) · Molecular and Cellular Biology · doi:10.1128/mcb.00171-22 · Cited by 131
Self-citationExtranuclear 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
Self-citationSenescent cells: Living or dying is a matter of NK cells
Antonangeli, F., Zingoni, A., Soriani, A., & Santoni, A. (2019) · Journal of Leukocyte Biology · doi:10.1002/jlb.mr0718-299r · Cited by 134
Putting the brakes on the cell cycle: mechanisms of cellular growth arrest
Pack, L. R., Daigh, L. H., & Meyer, T. (2019) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2019.05.005 · Cited by 139
Colucci, M., Sarill, M., Maddalena, M., Valdata, A., Troiani, M., Massarotti, M., Bolis, M., Bressan, S., Kohl, A., Robesti, D., et al. (2025) · Cancer Cell · doi:10.1016/j.ccell.2025.05.015 · Cited by 143
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
Meng, F., Yu, Z., Zhang, D., Chen, S., Guan, H., Zhou, R., Wu, Q., Zhang, Q. Y., Liu, S., Ramani, M. K. V., et al. (2021) · Molecular Cell · doi:10.1016/j.molcel.2021.07.040 · Cited by 130
Cindrova-Davies, T., Fogarty, N. M. E., Jones, C. J. P., Kingdom, J., & Burton, G. J. (2018) · Placenta · doi:10.1016/j.placenta.2018.06.307 · Cited by 127
“Recent evidence shows that the presence of DNA in the cytoplasm can initiate a SASP response by activating the innate immunity cytosolic DNA-sensing cyclic GMP-AMP synthase (cGAS)-STING pathway [16,17].”
BackgroundGuo, X., Ni, J., Liang, Z., Xue, J., Fenech, M. F., & Wang, X. (2018) · Mutation Research/Reviews in Mutation Research · doi:10.1016/j.mrrev.2018.11.001 · Cited by 127
Kang, C. (2019) · Europe PMC (PubMed Central) · doi:10.14348/molcells.2019.0298 · Cited by 129
The role of cGAS-STING signalling in liver diseases
Chen, R., Du, J., Zhu, H., & Ling, Q. (2021) · JHEP Reports · doi:10.1016/j.jhepr.2021.100324 · Cited by 131
Cellular senescence and cardiovascular diseases: moving to the “heart” of the problem
Evangelou, K., Vasileiou, P. V. S., Papaspyropoulos, A., Hazapis, O. G., Petty, R., Demaria, M., & Gorgoulis, V. G. (2022) · Physiological Reviews · doi:10.1152/physrev.00007.2022 · Cited by 127
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
SenNet Consortium, Writing Group, Lee, P. J., Benz, C. C., Blood, P., Börner, K., Campisi, J., Chen, F., Daldrup-Link, H., De Jager, P., et al. (2022) · Nature Aging · doi:10.1038/s43587-022-00326-5 · Cited by 122
Cellular senescence in lung cancer: Molecular mechanisms and therapeutic interventions
Jha, S. K., Rubis, G. D., Devkota, S. R., Zhang, Y., Adhikari, R., Jha, L. A., Bhattacharya, K., Mehndiratta, S., Gupta, G., Singh, S. K., et al. (2024) · Ageing Research Reviews · doi:10.1016/j.arr.2024.102315 · Cited by 138
Biochemistry, Cell Biology, and Pathophysiology of the Innate Immune cGAS–cGAMP–STING Pathway
Ritchie, C., Carozza, J. A., & Li, L. (2022) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-040320-101629 · Cited by 123
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
