COX2 regulates senescence secretome composition and senescence surveillance through PGE2
Open accessAbstract
Senescent cells trigger their own immune-mediated destruction, termed senescence surveillance. This is dependent on the inflammatory senescence-associated secretory phenotype (SASP), which includes COX2, an enzyme with complex roles in cancer. The role COX2 plays during senescence surveillance is unknown. Here, we show that during RAS-induced senescence (RIS), COX2 is a critical regulator of SASP composition and senescence surveillance in vivo . COX2 regulates the expression of multiple inflammatory SASP components through an autocrine feedback loop involving its downstream product, prostaglandin E2 (PGE 2 ), binding to EP4. During in vivo hepatocyte RIS, Cox2 is critical to tumor suppression, Cxcl1 expression, and immune-mediated senescence surveillance, partially through PGE 2 . Loss of Cox2 in RIS dysregulates the intrahepatic immune microenvironment, with enrichment of immunosuppressive immature myeloid cells and CD4 + regulatory T lymphocytes. Therefore, COX2 and PGE 2 play a critical role in senescence, shaping SASP composition, promoting senescence surveillance and tumor suppression in the earliest stages of tumorigenesis.
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
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?
These prostaglandins promote senescence and the SASP.
“These prostaglandins are known to promote senescence and the SASP135–137.”
From COVID-19 and cellular senescence (2023) · cites this paper as [136]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT Method
Livak, K. J., & Schmittgen, T. D. (2001) · Methods · doi:10.1006/meth.2001.1262 · Cited by 180,860 · see citing works
The Sequence Alignment/Map format and SAMtools
Li, H., Handsaker, B., Wysoker, A., Fennell, T., Ruan, J., Homer, N., Marth, G., Abecasis, G., Durbin, R., & 1000 Genome Project Data Processing Subgroup (2009) · Bioinformatics · doi:10.1093/bioinformatics/btp352 · Cited by 62,041 · see citing works
Subramanian, A., Tamayo, P., Mootha, V. K., Mukherjee, S., Ebert, B. L., Gillette, M. A., Paulovich, A., Pomeroy, S. L., Golub, T. R., Lander, E. S., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0506580102 · Cited by 53,625 · see citing works
STAR: ultrafast universal RNA-seq aligner
Dobin, A., Davis, C. A., Schlesinger, F., Drenkow, J., Zaleski, C., Jha, S., Batut, P., Chaisson, M., & Gingeras, T. R. (2013) · Bioinformatics · doi:10.1093/bioinformatics/bts635 · Cited by 51,709 · see citing works
Robinson, M. D., McCarthy, D. J., & Smyth, G. K. (2010) · Bioinformatics · doi:10.1093/bioinformatics/btp616 · Cited by 41,364 · see citing works
featureCounts: an efficient general purpose program for assigning sequence reads to genomic features
Liao, Y., Smyth, G. K., & Shi, W. (2014) · Bioinformatics · doi:10.1093/bioinformatics/btt656 · Cited by 27,219 · see citing works
ggplot2: Elegant Graphics for Data Analysis
Wickham, H. (2009) · doi:10.1007/978-0-387-98141-3 · Cited by 14,447 · see citing works
Mootha, V. K., Lindgren, C. M., Eriksson, K.-F., Subramanian, A., Sihag, S., Lehar, J., Puigserver, P., Carlsson, E., Ridderstråle, M., Laurila, E., et al. (2003) · Nature Genetics · doi:10.1038/ng1180 · Cited by 10,197 · see citing works
GENCODE: The reference human genome annotation for The ENCODE Project
Harrow, J., Frankish, A., Gonzalez, J. M., Tapanari, E., Diekhans, M., Kokocinski, F., Aken, B. L., Barrell, D., Zadissa, A., Searle, S., et al. (2012) · Genome Research · doi:10.1101/gr.135350.111 · Cited by 4,585 · see citing works
Mutation of the mouse klotho gene leads to a syndrome resembling ageing
Kuro-o, M., Matsumura, Y., Aizawa, H., Kawaguchi, H., Suga, T., Utsugi, T., Ohyama, Y., Kurabayashi, M., Kaname, T., Kume, E., et al. (1997) · Nature · doi:10.1038/36285 · Cited by 3,837 · see citing works
Preinvasive and invasive ductal pancreatic cancer and its early detection in the mouse
Hingorani, S. R., Petricoin, E. F., Maitra, A., Rajapakse, V., King, C., Jacobetz, M. A., Ross, S., Conrads, T. P., Veenstra, T. D., Hitt, B. A., et al. (2003) · Cancer Cell · doi:10.1016/s1535-6108(03)00309-x · Cited by 2,471 · see citing works
Accelerating t-SNE using tree-based algorithms
van der Maaten, L. (2014) · Journal of machine learning research · doi:10.5555/2627435.2697068 · Cited by 2,207 · 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
Böttcher, J. P., Bonavita, E., Chakravarty, P., Blees, H., Cabeza-Cabrerizo, M., Sammicheli, S., Rogers, N. C., Sahai, E., Zelenay, S., & Reis e Sousa, C. (2018) · Cell · doi:10.1016/j.cell.2018.01.004 · Cited by 1,857 · 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 18× · see citing works
“Similarly, inhibition of NF-kB function during RIS, through co-expression of an IkBaS32A / S36A ‘‘super-repressor’’ (SR), abrogates IL-6, IL-8, and COX2 expression (Figure 2A), reinforcing previous studies demonstrating COX2 expression to be NF-kB dependent in other contexts (Gallois et al., 1998).”
ResultInfluentialSenescence surveillance of pre-malignant hepatocytes limits liver cancer development
Kang, T.-W., Yevsa, T., Woller, N., Hoenicke, L., Wuestefeld, T., Dauch, D., Hohmeyer, A., Gereke, M., Rudalska, R., Potapova, A., et al. (2011) · Nature · doi:10.1038/nature10599 · Cited by 1,621 · see citing works
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
Regulation of Immune Responses by Prostaglandin E2
Kaliński, P. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1101029 · Cited by 1,477 · see citing works
Cyclooxygenase-Dependent Tumor Growth through Evasion of Immunity
Zelenay, S., van der Veen, A. G., Böttcher, J. P., Snelgrove, K. J., Rogers, N. C., Acton, S. E., Chakravarty, P., Girotti, M. R., Marais, R., Quezada, S. A., et al. (2015) · Cell · doi:10.1016/j.cell.2015.08.015 · Cited by 1,123 · see citing works
Chien, Y., Scuoppo, C., Wang, X., Fang, X., Balgley, B., Bolden, J. E., Premsrirut, P., Luo, W., Chicas, A., Lee, C. S., et al. (2011) · Genes & Development · doi:10.1101/gad.17276711 · Cited by 1,046 · see citing works
The DNA damage response induces inflammation and senescence by inhibiting autophagy of GATA4.
Kang, C., Xu, Q., Martin, T. D., Li, M. Z., Demaria, M., Aron, L., Lu, T., Yankner, B. A., Campisi, J., & Elledge, S. J. (2015) · Science · doi:10.1126/science.aaa5612 · Cited by 982 · see citing works
Cyclooxygenase‐2 in cancer: A review
Goradel, N. H., Najafi, M., Salehi, E., Farhood, B., & Mortezaee, K. (2018) · Journal of Cellular Physiology · doi:10.1002/jcp.27411 · Cited by 812 · see citing works
Non-Cell-Autonomous Tumor Suppression by p53
Lujambio, A., Akkari, L., Simon, J., Grace, D., Tschaharganeh, D. F., Bolden, J. E., Zhao, Z., Thapar, V., Joyce, J. A., Krizhanovsky, V., et al. (2013) · Cell · doi:10.1016/j.cell.2013.03.020 · Cited by 766 · cited 1× · see citing works
“, 2018), macrophages (Eggert et al., 2016; Kang et al., 2011; Lujambio et al., 2013) and natural killer (NK) cells (Sagiv et al.”
BackgroundOrjalo, A. V., Bhaumik, D., Gengler, B. K., Scott, G. K., & Campisi, J. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0905299106 · Cited by 654 · see citing works
A novel role for high-mobility group A proteins in cellular senescence and heterochromatin formation
Narita, M., Narita, M., Krizhanovsky, V., Nuñez, S., Chicas, A., Hearn, S. A., Myers, M. P., & Lowe, S. W. (2006) · Cell · doi:10.1016/j.cell.2006.05.052 · Cited by 629 · see citing works
Self-citationEggert, T., Wolter, K., Ji, J., Ma, C., Yevsa, T., Klotz, S., Medina-Echeverz, J., Longerich, T., Forgues, M., Reisinger, F., et al. (2016) · Cancer Cell · doi:10.1016/j.ccell.2016.09.003 · Cited by 609 · see citing works
Impaired immune surveillance accelerates accumulation of senescent cells and aging
Ovadya, Y., Landsberger, T., Leins, H., Vadai, E., Gal, H., Biran, A., Yosef, R., Sagiv, A., Agrawal, A., Shapira, A., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-07825-3 · Cited by 578 · see citing works
NOTCH1 mediates a switch between two distinct secretomes during senescence
Hoare, M., Ito, Y., Kang, T.-W., Weekes, M. P., Matheson, N. J., Patten, D. A., Shetty, S., Parry, A. J., Menon, S., Salama, R., et al. (2016) · Nature Cell Biology · doi:10.1038/ncb3397 · Cited by 522 · see citing works
Self-citationLoo, T. M., Kamachi, F., Watanabe, Y., Yoshimoto, S., Kanda, H., Arai, Y., Nakajima-Takagi, Y., Iwama, A., Koga, T., Sugimoto, Y., et al. (2017) · Cancer Discovery · doi:10.1158/2159-8290.cd-16-0932 · Cited by 478 · see citing works
Toso, A., Revandkar, A., Di Mitri, D., Guccini, I., Proietti, M., Sarti, M., Pinton, S., Zhang, J., Kalathur, M., Civenni, G., et al. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.08.044 · Cited by 418 · cited 2× · see citing works
“Therefore, it has become clear that rather than a singular secretome, there must exist sub-phenotypes to the SASP tailoring output to the cellular context (Hoare et al., 2016; Toso et al., 2014).”
BackgroundBRD4 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 · cited 3× · see citing works
“NK-cell chemotaxis experiments NK-cell chemotaxis experiments were performed and analyzed as described elsewhere (Tasdemir et al., 2016) with the following variations: NK cells were stained with the CellTracker Red CMTPX Dye (Thermo Fisher Scientific) (according to the manufacturer’s instructions) and then seeded into…”
BackgroundMethodInfluentialLun, A. T. L., Chen, Y., & Smyth, G. K. (2016) · Methods in molecular biology · doi:10.1007/978-1-4939-3578-9_19 · Cited by 413 · see citing works
Antagonistic Inflammatory Phenotypes Dictate Tumor Fate and Response to Immune Checkpoint Blockade
Bonavita, E., Bromley, C. P., Jonsson, G., Pelly, V. S., Sahoo, S., Walwyn-Brown, K., Mensurado, S., Moeini, A., Flanagan, E., Bell, C. R., et al. (2020) · Immunity · doi:10.1016/j.immuni.2020.10.020 · Cited by 252 · see citing works
Parks, D. R., Roederer, M., & Moore, W. (2006) · Cytometry Part A · doi:10.1002/cyto.a.20258 · Cited by 246 · see citing works
Granule exocytosis mediates immune surveillance of senescent cells
Sagiv, A., Biran, A., Yon, M., Simon, J., Lowe, S. W., & Krizhanovsky, V (2013) · Oncogene · doi:10.1038/onc.2012.206 · Cited by 240 · see citing works
Testing for differential abundance in mass cytometry data
Lun, A. T. L., Richard, A. C., & Marioni, J. C. (2017) · Nature Methods · doi:10.1038/nmeth.4295 · Cited by 181 · see citing works
Gallois, C., Habib, A., Tao, J., Moulin, S., Maclouf, J., Mallat, A., & Lotersztajn, S. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.36.23183 · Cited by 155 · see citing works
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 · see citing works
Carlson, C. M., Frandsen, J. L., Kirchhof, N., McIvor, R. S., & Largaespada, D. A. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0502974102 · Cited by 134 · see citing works
Dagouassat, M., Gagliolo, J.-M., Chrusciel, S., Bourin, M.-C., Duprez, C., Caramelle, P., Boyer, L., Hue, S., Stern, J.-B., Validire, P., et al. (2013) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201208-1361oc · Cited by 120 · see citing works
Cardiomyocyte cyclooxygenase-2 influences cardiac rhythm and function
Wang, D., Patel, V. V., Ricciotti, E., Zhou, R., Levin, M. D., Gao, E., Zhou, Y., Ferrari, V. A., Lu, M. M., Xu, J., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0805806106 · Cited by 116 · see citing works
NOTCH-mediated non-cell autonomous regulation of chromatin structure during senescence
Parry, A. J., Hoare, M., Bihary, D., Hänsel-Hertsch, R., Smith, S., Tomimatsu, K., Mannion, E., Smith, A., D’Santos, P., Russell, I. A., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-04283-9 · Cited by 102 · see citing works
Self-citationSerrão, E. M., Kettunen, M. I., Rodrigues, T. B., Dzien, P., Wright, A. J., Gopinathan, A., Gallagher, F. A., Lewis, D. Y., Frese, K. K., Almeida, J., et al. (2015) · Gut · doi:10.1136/gutjnl-2015-310114 · Cited by 87 · see citing works
T cell cytolytic capacity is independent of initial stimulation strength
Richard, A. C., Lun, A. T. L., Lau, W. W. Y., Göttgens, B., Marioni, J. C., & Griffiths, G. M. (2018) · Nature Immunology · doi:10.1038/s41590-018-0160-9 · Cited by 80 · see citing works
Kabir, T. D., Leigh, R. J., Tasena, H., Mellone, M., Coletta, R. D., Parkinson, E. K., Prime, S. S., Thomas, G. J., Paterson, I. C., Zhou, D., et al. (2016) · Aging · doi:10.18632/aging.100987 · Cited by 78 · see citing works
Normal or stress-induced fibroblast senescence involves COX-2 activity
Zdanov, S., Bernard, D., Debacq‐Chainiaux, F., Martien, S., Gosselin, K., Vercamer, C., Chelli, F., Toussaint, O., & Abbadie, C. (2007) · Experimental Cell Research · doi:10.1016/j.yexcr.2007.04.033 · Cited by 68 · see citing works
Na, Y. R., Jung, D., Yoon, B. R., Lee, W., & Seok, S. H. (2015) · European Journal of Immunology · doi:10.1002/eji.201545471 · Cited by 51 · see citing works
The Power Behind the Throne: Senescence and the Hallmarks of Cancer
Hoare, M., & Narita, M. (2017) · Annual Review of Cancer Biology · doi:10.1146/annurev-cancerbio-030617-050352 · Cited by 31 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Cellular senescence: the good, the bad and the unknown
Huang, W., Hickson, L. J., Eirin, A., Kirkland, J. L., & Lerman, L. O. (2022) · Nature Reviews Nephrology · doi:10.1038/s41581-022-00601-z · Cited by 1,150 · 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
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 · see citing works
Lipids and lipid metabolism in cellular senescence: Emerging targets for age-related diseases
Zeng, Q., Gong, Y., Zhu, N., Shi, Y., Zhang, C., & Li, Q. (2024) · Ageing Research Reviews · doi:10.1016/j.arr.2024.102294 · Cited by 188 · see citing works
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 · see citing works
Senescence 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 138 · see citing works
Bell, C. R., Pelly, V. S., Moeini, A., Chiang, S., Flanagan, E., Bromley, C. P., Clark, C. I., Earnshaw, C. H., Koufaki, M. A., Bonavita, E., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-29606-9 · Cited by 141 · see citing works
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 130 · see citing works
How good is the evidence that cellular senescence causes skin ageing?
Low, E., Alimohammadiha, G., Smith, L. A., Costello, L., Przyborski, S. A., von Zglinicki, T., & Miwa, S. (2021) · Ageing Research Reviews · doi:10.1016/j.arr.2021.101456 · Cited by 114 · see citing works
Emerging role of aging in the progression of NAFLD to HCC
He, Y., Su, Y., Duan, C., Wang, S., He, W. G., Zhang, Y., An, X., & He, M. (2022) · Ageing Research Reviews · doi:10.1016/j.arr.2022.101833 · Cited by 98 · see citing works
Giroud, J., Bouriez, I., Paulus, H., Pourtier, A., Debacq‐Chainiaux, F., & Pluquet, O. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241310788 · Cited by 77 · see citing works
Senescence-induced endothelial phenotypes underpin immune-mediated senescence surveillancePreprint
Yin, K., Patten, D. A., Gough, S., Gonçalves, S. D. B., Chan, A. S. L., Olan, I., Cassidy, L. D., Poblocka, M., Zhu, H., Lun, A. T. L., et al. (2022) · Genes & Development · doi:10.1101/gad.349585.122 · Cited by 75 · see citing works
Self-citationCellular Plasticity: A Route to Senescence Exit and Tumorigenesis
Blander, H. D., Morel, A., Senaratne, A. P., Ouzounova, M., & Puisieux, A. (2021) · Cancers · doi:10.3390/cancers13184561 · Cited by 74 · see citing works
Sharma, R., Kumar, R., Sharma, A., Goel, A., & Padwad, Y. S. (2022) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2022.109068 · Cited by 76 · see citing works
p53 in senescence – it's a marathon, not a sprint
Sheekey, E., & Narita, M. (2021) · FEBS Journal · doi:10.1111/febs.16325 · Cited by 63 · see citing works
Self-citationCellular senescence in the tumor microenvironment and context‐specific cancer treatment strategies
Yasuda, T., Baba, H., & Ishimoto, T. (2021) · FEBS Journal · doi:10.1111/febs.16231 · Cited by 52 · see citing works
Translating the Biology of Aging into New Therapeutics for Alzheimer's Disease: Senolytics
Rießland, M., & Orr, M. E. (2023) · The Journal of Prevention of Alzheimer s Disease · doi:10.14283/jpad.2023.104 · Cited by 55 · see citing works
Chen, J., Deng, J. C., Zemans, R. L., Bahmed, K., Kośmider, B., Zhang, M., Peters-Golden, M. L., & Goldstein, D. R. (2022) · Nature Communications · doi:10.1038/s41467-022-34593-y · Cited by 48 · see citing works
Cellular senescence in cancer: molecular mechanisms and therapeutic targets
Jin, P., Duan, X., Li, L., Zhou, P., Zou, C., & Xie, K. (2024) · MedComm · doi:10.1002/mco2.542 · Cited by 46 · see citing works
Roda, E., Luca, F. D., Ratto, D., Priori, E. C., Savino, E., Bottone, M. G., & Rossi, P. (2023) · Biology · doi:10.3390/biology12020196 · Cited by 43 · see citing works
Gao, Z., Bravo, R., Rupert, J. E., Drunen, R. V., Yu, Y., Eckel‐Mahan, K. L., & Kolonin, M. G. (2024) · Aging Cell · doi:10.1111/acel.14138 · Cited by 34 · see citing works
Titration of RAS alters senescent state and influences tumour initiation
Chan, A. S. L., Zhu, H., Narita, M., Cassidy, L. D., Young, A. R. J., Bermejo‐Rodríguez, C., Janowska, A. T., Chen, H., Gough, S., Oshimori, N., et al. (2024) · Nature · doi:10.1038/s41586-024-07797-z · Cited by 34 · see citing works
Self-citationSenescent cells and SASP in cancer microenvironment: New approaches in cancer therapy
Özdemir, A., Demir, Y. D. Ş., Yeşilyurt, Z. E., & Ark, M. (2022) · Advances in protein chemistry and structural biology · doi:10.1016/bs.apcsb.2022.10.002 · Cited by 33 · see citing works
Senescence of Hepatic Stellate Cells by Specific Delivery of Manganese for Limiting Liver Fibrosis
Gu, L., Zhao, C., Wang, Y., Wang, C., Yin, X., Ye, Q., Liu, Y., Zou, X., Wang, L., Zhuge, Y., et al. (2024) · Nano Letters · doi:10.1021/acs.nanolett.3c03689 · Cited by 32 · see citing works
Liu, Y., Sun, X., Wang, L., Dou, Y., Tian, Y., Yu, T., Zhang, Y., Zhao, Q., Lu, J., Feng, Y., et al. (2024) · Advanced Materials · doi:10.1002/adma.202408678 · Cited by 29 · see citing works
c-Jun N-terminal kinase signaling in cellular senescence
Deng, Y., Adam, V., Nepovimová, E., Heger, Z., Valko, M., Wu, Q., Wei, W., & Kuča, K. (2023) · Archives of Toxicology · doi:10.1007/s00204-023-03540-1 · Cited by 28 · see citing works
Ma, Y., Jiang, J., Zhao, C., Wei, B., & Gao, J. (2025) · Hepatology Communications · doi:10.1097/hc9.0000000000000802 · Cited by 28 · see citing works
Wang, J., Zhou, X., Yu, P., Yao, J., Guo, P., Xu, Q., Zhao, Y., Wang, G., Li, Q., Zhu, X., et al. (2025) · Nature Aging · doi:10.1038/s43587-025-00886-2 · Cited by 28 · see citing works
Tumor Secretome to Adoptive Cellular Immunotherapy: Reduce Me Before I Make You My Partner
Etxebeste-Mitxeltorena, M., del Rincón-Loza, I., & Martín-Antonio, B. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.717850 · Cited by 25 · see citing works
Lipids and the hallmarks of ageing: From pathology to interventions
Sharma, R., & Diwan, B. (2023) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2023.111858 · Cited by 26 · see citing works
Alessio, N., Aprile, D., Peluso, G., Mazzone, V., Patrone, D., Bernardo, G. D., & Galderisi, U. (2024) · Cell Communication and Signaling · doi:10.1186/s12964-024-01469-1 · Cited by 26 · see citing works
Meiners, F., Hinz, B., Boeckmann, L., Secci, R., Sueto, S. O. B., Kuepfer, L., Fuellen, G., & Barrantes, I. (2024) · Scientific Reports · doi:10.1038/s41598-024-55870-4 · Cited by 21 · see citing works
Garbarino, V. R., Palavicini, J. P., Melendez, J., Barthelemy, N. R., He, Y., Kautz, T. F., Lopez-Cruzan, M., Mathews, J. J., Xu, P., Zhang, B., et al. (2025) · Neurotherapeutics · doi:10.1016/j.neurot.2025.e00591 · Cited by 19 · see citing works
Venkataraman, A., Kordic, I., Li, J., Zhang, N. Y., Bharadwaj, N. S., Fang, Z., Das, S., & Coskun, A. F. (2024) · npj Aging · doi:10.1038/s41514-024-00178-w · Cited by 22 · see citing works
SEPDB: a database of secreted proteins
Wang, R., Ren, C., Gao, T., Li, H., Bo, X., Zhu, D., Zhang, D., Chen, H., & Zhang, Y. (2024) · Database · doi:10.1093/database/baae007 · Cited by 18 · see citing works
Frey, Y., Haj, M., Ziv, Y., Elkon, R., & Shiloh, Y. (2024) · Nucleic Acids Research · doi:10.1093/nar/gkae1257 · Cited by 18 · see citing works
Salminen, A., Kaarniranta, K., & Kauppinen, A. (2025) · Biogerontology · doi:10.1007/s10522-025-10268-1 · Cited by 21 · see citing works
The Potential of Senescence as a Target for Developing Anticancer Therapy
Jo, H., Shim, K., & Jeoung, D. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24043436 · Cited by 17 · see citing works
Aging of lymphoid stromal architecture impacts immune responses
Lancaster, J. N. (2023) · Seminars in Immunology · doi:10.1016/j.smim.2023.101817 · Cited by 16 · see citing works
Role of exosome-derived miRNAs in diabetic wound angiogenesis
Chen, W., Luo, Y., Chen, X., & Xiao, J. (2023) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-023-04874-1 · Cited by 14 · see citing works
Senescence Promotes the Recovery of Stemness among Cancer Cells via Reprograming
Wang, D., & Liu, L. (2024) · Biomolecules · doi:10.3390/biom14030288 · Cited by 14 · see citing works
Li, Y., Sun, R., Lai, C., Liu, K., Yang, H., Peng, Z., Xu, D., Huang, F., Tang, K., Peng, Y., et al. (2024) · Journal of Translational Medicine · doi:10.1186/s12967-024-05317-1 · Cited by 17 · see citing works
Midazolam alleviates cellular senescence in SH‐SY5Y neuronal cells in Alzheimer's disease
Wang, P., Wang, P., Luan, H., Wu, Y., & Chen, Y. (2022) · Brain and Behavior · doi:10.1002/brb3.2822 · Cited by 12 · see citing works
Wang, Y., Lin, J., Yu, Z., Cheng, J., Cheng, J., & Cui, W. (2024) · Colloids and Surfaces B Biointerfaces · doi:10.1016/j.colsurfb.2024.113772 · Cited by 10 · see citing works
Systematic transcriptomic analysis and temporal modelling of human fibroblast senescence
Scanlan, R.-L., Pease, L., O’Keefe, H., Guimera, A. M., Rasmussen, L. J., Wordsworth, J., & Shanley, D. P. (2024) · Frontiers in Aging · doi:10.3389/fragi.2024.1448543 · Cited by 11 · see citing works
Chen, C., Chen, F., Gu, L., Jiang, Y., Cai, Z., Zhao, Y., Chen, L., Zhu, Z., & Liu, X. (2024) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2024.117919 · Cited by 9 · see citing works
Xue, S., Ge, W., Wang, K., Mao, T., Zhang, X., Xu, H., Wang, Y., Yao, J., Li, S., Yue, M., et al. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.942225 · Cited by 9 · see citing works
Zhong, H., Chang, L., Pei, S., Kang, Y., Yang, L., Wu, Y., Chen, N., Luo, Y., Zhou, Y., Xie, J., et al. (2024) · Aging · doi:10.18632/aging.205544 · Cited by 8 · see citing works
Senescent CD4+ T cells and autoimmune diseases: mechanisms and therapeutic prospects
Hu, Y., He, L., & Long, H. (2025) · Autoimmunity Reviews · doi:10.1016/j.autrev.2025.103957 · Cited by 8 · see citing works
Orr, M. E., Garbarino, V. R., Palavicini, J., Melendez, J., Barthélemy, N. R., He, Y., Kautz, T. F., Lopez‐Cruzan, M., Mathews, J. J., Xu, P., et al. (2024) · Research Square · doi:10.21203/rs.3.rs-3994894/v1 · Cited by 8 · see citing works
Immune therapeutic strategies for the senescent tumor microenvironment
Yasuda, T., & Wang, Y. (2024) · British Journal of Cancer · doi:10.1038/s41416-024-02865-7 · Cited by 7 · see citing works
Campos, J., Sampaio‐Marques, B., Santos, D. J., Barata‐Antunes, S., Ribeiro, M. A., Serra, S. C., Pinho, T. S., Canto-Gomes, J., Marote, A., Cortez, M., et al. (2024) · Tissue Engineering and Regenerative Medicine · doi:10.1007/s13770-024-00679-5 · Cited by 7 · see citing works
Zhelavskyi, M. M., Kernychnyi, S., Dmytriv, O. Y., & Betlinska, T. V. (2022) · Ukrainian Journal of Veterinary and Agricultural Sciences · doi:10.32718/ujvas5-1.02 · Cited by 7 · see citing works
Arya, M., Rathour, K. S., Tiwari, A., Chauhan, V. S., & Taj, G. (2022) · Annals of Phytomedicine An International Journal · doi:10.54085/ap.2022.11.1.41 · Cited by 7 · see citing works
Zhang, Z., Deng, Y., Chen, J., Li, C., Dai, X., Wang, C., Pengfei, S., Li, S., Jiang, H., & Pan, B. (2025) · Ecotoxicology and Environmental Safety · doi:10.1016/j.ecoenv.2025.119327 · Cited by 5 · see citing works
Chan, L., Tseng, Y., Wang, H., Chien, C., Wu, C., Wang, L., & Liang, C. (2023) · Journal of Cancer · doi:10.7150/jca.82300 · Cited by 5 · see citing works
Exosomal dynamics: Bridging the gap between cellular senescence and cancer therapy
Aswani, B. S., Sajeev, A., Hegde, M., Mishra, A., Abbas, M., Vayalpurayil, T., Sethi, G., & Kunnumakkara, A. B. (2025) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2025.112045 · Cited by 5 · see citing works
Secreted HLA-Fc fusion profiles immunopeptidome in hypoxic PDAC and cellular senescence
Rettko, N. J., Kirkemo, L. L., & Wells, J. A. (2023) · PNAS Nexus · doi:10.1093/pnasnexus/pgad400 · Cited by 5 · see citing works
Mosaic Regulation of Stress Pathways Underlies Senescent Cell HeterogeneityPreprint
Avelar, R. A., Duffield, T., Lagger, C., Krstevska, N., Breuer, M., & de Magalhães, J. P. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.10.03.616489 · Cited by 5 · see citing works
Effects of Chlorogenic Acid on Cellular Senescence in an In Vitro Model of 3T3-L1 Murine Adipocytes
Molonia, M. S., Salamone, F. L., Trischitta, S., Saija, A., Cimino, F., & Speciale, A. (2026) · Molecules · doi:10.3390/molecules31010167 · Cited by 4 · see citing works
Giroud, J., Combémorel, E., Pourtier, A., Abbadie, C., & Pluquet, O. (2025) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00091.2025 · Cited by 6 · see citing works
Srour, E., Martin, N., Drullion, C., de Schutter, C., Giroud, J., Pioger, A., Deslé, J., Saas, L., Nassour, J., Théry, J., et al. (2024) · Aging · doi:10.18632/aging.206149 · Cited by 4 · see citing works
Cellular senescence and nanoparticle-based therapies: Current developments and perspectives
Henschke, A., Mielcarek, A., Grześkowiak, B. F., Perrigue, P. M., Jaskot, K., Coy, E. L., & Moya, S. E. (2024) · Nanotechnology Reviews · doi:10.1515/ntrev-2023-0211 · Cited by 5 · see citing works
da Silva, G. C., Diniz, T. F., Aires, R. D., Peruchetti, D. B., da Silva, R., Vieira, M. A. R., & Lemos, V. S. (2025) · Gerontology · doi:10.1159/000547620 · Cited by 3 · see citing works
Inflammation-associated long non-coding RNA signature in radicular cyst tissues
Bozgeyi̇k, E., Eğe, B., Erdoğmuş, Z., Bozgeyik, İ., Koparal, M., BAYAZIT, Ş., & Kurt, M. Y. (2023) · Pathology - Research and Practice · doi:10.1016/j.prp.2023.154456 · Cited by 3 · see citing works
Zhang, Y., Li, F., Ji, X., Shao, L., Lyu, Q., & Shao, Q. (2025) · Toxicon · doi:10.1016/j.toxicon.2025.108588 · Cited by 3 · see citing works
Solarska‐Ściuk, K., Kapavarapu, R., Poliszak, Z., Wnuk, M., & Lewińska, A. (2026) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2026.112033 · Cited by 2 · see citing works
Jipeng, E., Qiang, E., & Zhou, G. (2026) · PeerJ · doi:10.7717/peerj.20598 · Cited by 2 · see citing works
The rise of RAS: how gradual oncogene activation shapes the OIS spectrumPreprint
Zhu, H., Chan, A. S. L., & Narita, M. (2025) · Genes & Development · doi:10.1101/gad.352761.125 · Cited by 2 · see citing works
Self-citationcPLA2α-driven Cox-2/PGE2 axis promotes hypoxia-induced senescence in Jurkat T cells
Jung, J., Yang, Y., & Kim, Y. (2025) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2025.152894 · Cited by 1 · see citing works
Xu, Z., Guo, J., Liu, Z., Yu, J., Yuan, R., Min, Y., Wei, Z., & Peng, X. (2026) · Ageing Research Reviews · doi:10.1016/j.arr.2026.103270 · Cited by 1 · see citing works
Tsouri, E., Athanasopoulou, N., Akkari, L., & Vegna, S. (2026) · Seminars in Immunology · doi:10.1016/j.smim.2026.102053 · Cited by 1 · see citing works
Systematic transcriptomic analysis and temporal modelling of the senescent human fibroblastPreprint
Scanlan, R.-L., Pease, L., O’Keefe, H., Guimera, A. M., Shanley, D., & Wordsworth, J. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.08.16.504144 · Cited by 1 · see citing works
Expert system for LAN media selection
Johnson, M. L., Bratten, W. A., Williams, J. M. J., & Emrich, M. L. (1988) · OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information)
Lu, Y., Zhang, C., Wu, B., Guo, J., Fan, D., Wang, G., Zhang, W., Lin, L., Xu, X., Du, X., et al. (2025) · Journal of Hazardous Materials · doi:10.1016/j.jhazmat.2025.137914
Li, Y., Sun, R., Lai, C., Liu, K., 杨慧湘, Peng, Z., Xu, D., Huang, F., Tang, K., Peng, Y., et al. (2024) · Figshare · doi:10.6084/m9.figshare.25940231
Alessio, N., Aprile, D., Peluso, G., Mazzone, V., Patrone, D., Di Bernardo, G., & Galderisi, U. (2024) · Figshare · doi:10.6084/m9.figshare.25216796
Alessio, N., Aprile, D., Peluso, G., Mazzone, V., Patrone, D., Bernardo, G. D., & Galderisi, U. (2024) · Figshare · doi:10.6084/m9.figshare.26680358
Alessio, N., Aprile, D., Peluso, G., Mazzone, V., Patrone, D., Di Bernardo, G., & Galderisi, U. (2024) · Figshare · doi:10.6084/m9.figshare.26680355
Alessio, N., Aprile, D., Peluso, G., Mazzone, V., Patrone, D., Bernardo, G. D., & Galderisi, U. (2024) · Figshare · doi:10.6084/m9.figshare.26680352
Alessio, N., Aprile, D., Peluso, G., Mazzone, V., Patrone, D., Bernardo, G. D., & Galderisi, U. (2024) · Figshare · doi:10.6084/m9.figshare.25217314
Li, Y., Sun, R., Lai, C., Liu, K., 杨慧湘, Peng, Z., Xu, D., Huang, F., Tang, K., Peng, Y., et al. (2024) · Figshare · doi:10.6084/m9.figshare.25940031
Alessio, N., Aprile, D., Peluso, G., Mazzone, V., Patrone, D., Bernardo, G. D., & Galderisi, U. (2024) · Figshare · doi:10.6084/m9.figshare.26680349
The resolvin D and E biogenesis pathway regulates senescence and ageingPreprint
Mira-Carnicer, M., Menendez-Garcia, M., Merino-Navarro, A., Palomino-Lozano, C., Anton-Barros, C., Palmero, I., Malaspina, A., Montesinos, J., & O’Loghlen, A. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.01.26.701588
Lagni, A., Lotti, V., Cecchetto, R., Tonon, E., Diani, E., Palmisano, A., Piccaluga, P. P., Calgaro, M., Vitulo, N., Sorio, C., et al. (2026) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2026.1754083
Lipid metabolic reprogramming regulates macrophage senescence in the tumor microenvironment
Liu, Y., Li, C., Wang, J., Gao, M., & Jiang, S. (2026) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2026.04.002
Doxorubicin induces a reversible senescence-like state in the EPC fish cell line
Lee, K., & Futami, K. (2026) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2026.153881
Burkett, J. B., FUHR, J., Falk, A. C., Dadi, P. K., Bene, A. N. D., LUCERNE, A., McNitt, D. H., Clark, L. M., Maxwell, M., Gaeth, V. A., et al. (2026) · Diabetes · doi:10.2337/db25-1007
de Azevedo, V. R., Guimarães, I. D. S., Farrapo, M. J., Martins-Cardoso, K., de Melo, A. C., Monteiro, R. Q., & Almeida, V. H. (2026) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2026.168443
Pallatt, S., Nambidi, S., Banerjee, A., & Pathak, S. (2026) · Cancer Reports · doi:10.1002/cnr2.70682
Yin, Y., Chen, H., Xie, W., Wang, Y., Qian, Y., Sheng, R., Li, D., Li, J., Zhou, X., Dai, Z., et al. (2026) · EMBO Molecular Medicine · doi:10.1038/s44321-026-00521-6
Zhang, J., Su, W., Duan, J., Sun, Y., & Liu, B. (2026) · The Innovation Life · doi:10.59717/j.xinn-life.2026.100262
The Senescence-Malignancy Axis: An Inflammaging Perspective
Patrono, I., Sonnessa, M., Trerotola, M., Giudetti, A. M., Summa, S. D., Zito, F. A., Saponaro, C., & Vergara, D. (2026) · Antioxidants · doi:10.3390/antiox15101357
Geng, X., Li, P., Xu, K., Yang, S., & Hu, X. (2026) · Molecular Biology Reports · doi:10.1007/s11033-026-13049-2
- Authors
- Gonçalves, S., Yin, K., Ito, Y., Chan, A., Olan, I., Gough, S., Cassidy, L., Serrao, E., Smith, S., Young, A., Narita, M., & Hoare, M.
- Affiliations
- University of Cambridge (GB)
- Tokyo Institute of Technology (JP)
- Corresponding author
- Hoare, Matthew
- ORCID
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2021-03
- Volume
- 34
- Issue
- 11
- Pages
- 108860
- ISSN
- 2211-1247 (ISSN-L)
- PMC
- PMC7972992
- OpenAlex
- W3136839549
- Cited by
- 95
- References
- 48
- Citations by year
- 2026: 16 · 2025: 15 · 2024: 32 · 2023: 11 · 2022: 14 · 2021: 6
- FWCI
- 9.90
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Apollo (University of Cambridge) (submittedVersion)
- Apollo
- Funders
- Medical Research Council (MR/R010013/1)
- Biotechnology and Biological Sciences Research Council (BB/S013466/1)
- Cancer Research UK (C52489/A19924)
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Pharmacology › Inflammatory mediators and NSAID effects
- Keywords
- cyclooxygenase-2, senescence-associated secretory phenotype, prostaglandin E2, EP4 receptor, Ras-induced senescence, hepatocyte senescence, tumor suppression, CXCL1, regulatory T cells, myeloid-derived suppressor cells, tumor immune microenvironment, carcinogenesis
- MeSH terms
- Senescence-Associated Secretory Phenotype, Secretome, Animals, Female, Fibroblasts, Humans, Mice, Inbred C57BL, Dinoprostone, Up-Regulation, Cellular Senescence, Mice, Cyclooxygenase 2, Cyclooxygenase 2 Inhibitors, Receptors, Prostaglandin E, EP4 Subtype, Tumor Microenvironment
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
