A Senescence-Inflammatory Switch from Cancer-Inhibitory to Cancer-Promoting Mechanism
Open accessAbstract
Senescence, perceived as a cancer barrier, is paradoxically associated with inflammation, which promotes tumorigenesis. Here, we characterize a distinct low-grade inflammatory process in stressed epithelium that is related to para-inflammation; this process either represses or promotes tumorigenesis, depending on p53 activity. Csnk1a1 (CKIα) downregulation induces a senescence-associated inflammatory response (SIR) with growth arrest in colorectal tumors, which loses its growth control capacity in the absence of p53 and instead, accelerates growth and invasiveness. Corresponding processes occur in CKIα-deleted intestinal organoids, assuming tumorigenic transformation properties ex vivo, upon p53 loss. Treatment of organoids and mice with anti-inflammatory agents suppresses the SIR and prevents p53-deficient organoid transformation and mouse carcinogenesis. SIR/para-inflammation suppression may therefore constitute a key mechanism in the anticarcinogenic effects of nonsteroidal anti-inflammatory drugs.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
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?
Even in the same tissue, the same triggers can either suppress tumorigenesis by inducing senescence or promote tumorigenesis, as in cytokine-induced senescence.
“Even in the same tissue, the same triggers can either suppress (by inducing senescence) or promote tumorigenesis, as in the case for cytokine-induced senescence 128,143”
From Inside and out: the activities of senescence in cancer (2014) · cites this paper as [143]
Cites
Hallmarks of Cancer: The Next Generation
Hanahan, D., & Weinberg, R. A. (2011) · Cell · doi:10.1016/j.cell.2011.02.013 · Cited by 66,590 · 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
Coussens, L. M., & Werb, Z. (2002) · Nature · doi:10.1038/nature01322 · Cited by 15,111 · see citing works
TopHat: discovering splice junctions with RNA-Seq
Trapnell, C., Pachter, L. S., & Salzberg, S. L. (2009) · Bioinformatics · doi:10.1093/bioinformatics/btp120 · Cited by 11,477 · see citing works
A biomarker that identifies senescent human cells in culture and in aging skin in vivo.
Dimri, G. P., Lee, X., Basile, G., Acosta, M., Scott, G., Roskelley, C., Medrano, E. E., Linskens, M., Rubelj, I., & Pereira-Smith, O. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.20.9363 · Cited by 7,477 · see citing works
Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche
Sato, T., Vries, R. G., Snippert, H. J., van de Wetering, M., Barker, N., Stange, D. E., van Es, J. H., Abo, A., Kujala, P., Peters, P. J., et al. (2009) · Nature · doi:10.1038/nature07935 · Cited by 7,204 · see citing works
Origin and physiological roles of inflammation
Medzhitov, R. (2008) · Nature · doi:10.1038/nature07201 · Cited by 6,618 · see citing works
The senescence-associated secretory phenotype: the dark side of tumor suppression
Coppé, J.-P., Desprez, P.-Y., Krtolica, A., & Campisi, J. (2010) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev-pathol-121808-102144 · Cited by 5,206 · see citing works
Tumors: Wounds That Do Not Heal
Flier, J. S., Underhill, L. H., & Dvorak, H. F. (1986) · New England Journal of Medicine · doi:10.1056/nejm198612253152606 · Cited by 4,391 · cited 1× · see citing works
“Tumors have many characteristics in common with wound healing and indeed were described as ‘‘wounds that won’t heal’’ (Dvorak, 1986).”
BackgroundSato, T., Stange, D. E., Ferrante, M., Vries, R. G. J., van Es, J. H., van den Brink, S., van Houdt, W. J., Pronk, A., van Gorp, J., Siersema, P. D., et al. (2011) · Gastroenterology · doi:10.1053/j.gastro.2011.07.050 · Cited by 3,753 · see citing works
p21 in cancer: Intricate networks and multiple activities
Abbas, T., & Dutta, A. (2009) · Nature Reviews Cancer · doi:10.1038/nrc2657 · Cited by 2,712 · see citing works
DNA damage response as a candidate anti-cancer barrier in early human tumorigenesis
Bartkova, J., Hořejší, Z., Koed, K., Krämer, A., Tort, F., Zieger, K., Guldberg, P., Sehested, M., Nesland, J. M., Lukas, C., et al. (2005) · Nature · doi:10.1038/nature03482 · Cited by 2,688 · see citing works
Senescence and tumour clearance is triggered by p53 restoration in murine liver carcinomas
Xue, W., Zender, L., Miething, C., Dickins, R. A., Hernando, E., Krizhanovsky, V., Cordon-Cardo, C., & Lowe, S. W. (2007) · Nature · doi:10.1038/nature05529 · Cited by 2,473 · see citing works
IKKβ Links Inflammation and Tumorigenesis in a Mouse Model of Colitis-Associated Cancer
Greten, F. R., Eckmann, L., Greten, T. F., Park, J. M., Li, Z.-W., Egan, L. J., Kagnoff, M. F., & Karin, M. (2004) · Cell · doi:10.1016/j.cell.2004.07.013 · Cited by 2,433 · 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
Crucial role of p53-dependent cellular senescence in suppression of Pten-deficient tumorigenesis
Chen, Z., Trotman, L. C., Shaffer, D., Lin, H.-K., Dotan, Z. A., Niki, M., Koutcher, J. A., Scher, H. I., Ludwig, T., Gerald, W., et al. (2005) · Nature · doi:10.1038/nature03918 · Cited by 1,993 · see citing works
Oncogene-induced senescence is part of the tumorigenesis barrier imposed by DNA damage checkpoints
Bartkova, J., Rezaei, N., Liontos, M., Karakaidos, P., Kletsas, D., Issaeva, N., Vassiliou, L.-V. F., Kolettas, E., Niforou, K., Zoumpourlis, V. C., et al. (2006) · Nature · doi:10.1038/nature05268 · Cited by 1,986 · see citing works
Restoration of p53 function leads to tumour regression in vivo
Ventura, A., Kirsch, D. G., McLaughlin, M. E., Tuveson, D. A., Grimm, J., Lintault, L., Newman, J., Reczek, E. E., Weissleder, R., & Jacks, T. (2007) · Nature · doi:10.1038/nature05541 · Cited by 1,820 · 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 8× · see citing works
“…Gut Triggers a Distinct, Low-Grade Senescence-Associated Inflammatory Response Cellular senescence has distinct inflammatory features that function both to maintain the process via an autocrine loop (Bartek et al., 2008) and to affect neighboring cells via paracrine signaling (Acosta et al., 2008).”
BackgroundMethodInfluentialKrtolica, A., Parrinello, S., Lockett, S., Desprez, P.-Y., & Campisi, J. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.211053698 · Cited by 1,730 · see citing works
Cellular senescence in cancer and aging.
Collado, M., Blasco, M. A., & Serrano, M. (2007) · Cell · doi:10.1016/j.cell.2007.07.003 · Cited by 1,708 · see citing works
Senescence surveillance of pre-malignant hepatocytes limits liver cancer development
Kang, T.-W., Yevsa, T., Woller, N., Hoenicke, L., Wuestefeld, T., Dauch, D., Hohmeyer, A., Gereke, M., Rudalska, R., Potapova, A., et al. (2011) · Nature · doi:10.1038/nature10599 · Cited by 1,621 · see citing works
Inflammation meets cancer, with NF-κB as the matchmaker
Ben‐Neriah, Y., & Karin, M. (2011) · Nature Immunology · doi:10.1038/ni.2060 · Cited by 1,379 · see citing works
Self-citationRothwell, P. M., Wilson, M., Elwin, C.-E., Norrving, B., Algra, A., Warlow, C. P., & Meade, T. W. (2010) · The Lancet · doi:10.1016/s0140-6736(10)61543-7 · Cited by 1,351 · see citing works
Greenhough, A., Smartt, H. J. M., Moore, A. E., Roberts, H. R., Williams, A. C., Paraskeva, C., & Kaidi, A. (2009) · Carcinogenesis · doi:10.1093/carcin/bgp014 · Cited by 1,220 · see citing works
IAP Antagonists Induce Autoubiquitination of c-IAPs, NF-κB Activation, and TNFα-Dependent Apoptosis
Varfolomeev, E., Blankenship, J. W., Wayson, S. M., Fedorova, A. V., Kayagaki, N., Garg, P., Zobel, K., Dynek, J. N., Elliott, L. O., Wallweber, H. J. A., et al. (2007) · Cell · doi:10.1016/j.cell.2007.10.030 · Cited by 1,218 · see citing works
Self-citationSenescence in tumours: evidence from mice and humans
Collado, M., & Serrano, M. (2010) · Nature Reviews Cancer · doi:10.1038/nrc2772 · Cited by 1,124 · cited 1× · see citing works
“It is likely that CKIa ablation as a single genetic alteration may in fact mimic the cumulative effect of multiple genetic alterations in human colorectal cancer, many of which, like the Ras pathway mutations, culminate in DDR and senescence (Collado and Serrano, 2010; Figure 8).”
BackgroundBurn, J., Gerdes, A., Macrae, F., Mecklin, J., Möslein, G., Olschwang, S., Eccles, D., Evans, D. G., Maher, E. R., Bertario, L., et al. (2011) · The Lancet · doi:10.1016/s0140-6736(11)61049-0 · Cited by 947 · see citing works
Senescence-messaging secretome: SMS-ing cellular stress
Kuilman, T., & Peeper, D. S. (2009) · Nature Reviews Cancer · doi:10.1038/nrc2560 · Cited by 909 · see citing works
The role of COX-2 in intestinal inflammation and colorectal cancer
Wang, D., & DuBois, R. N. (2009) · Oncogene · doi:10.1038/onc.2009.421 · Cited by 893 · see citing works
Ras-induced interleukin-8 expression plays a critical role in tumor growth and angiogenesis
Sparmann, A., & Bar‐Sagi, D. (2004) · Cancer Cell · doi:10.1016/j.ccr.2004.09.028 · Cited by 854 · see citing works
Aspirin Use and Survival After Diagnosis of Colorectal Cancer
Chan, A. T. (2009) · JAMA · doi:10.1001/jama.2009.1112 · Cited by 554 · see citing works
Guerra, C., Collado, M., Navas, C., Schuhmacher, A. J., Hernández-Porras, I., Cañamero, M., Rodriguez-Justo, M., Serrano, M., & Barbacid, M. (2011) · Cancer Cell · doi:10.1016/j.ccr.2011.05.011 · Cited by 516 · see citing works
Liu, D., & Hornsby, P. J. (2007) · Cancer Research · doi:10.1158/0008-5472.can-06-3452 · Cited by 499 · see citing works
Coppé, J.-P., Patil, C. K., Rodier, F., Krtolica, A., Beauséjour, C. M., Parrinello, S., Hodgson, J. G., Chin, K., Desprez, P.-Y., & Campisi, J. (2010) · PLoS ONE · doi:10.1371/journal.pone.0009188 · Cited by 455 · see citing works
Pro-senescence therapy for cancer treatment
Nardella, C., Clohessy, J. G., Alimonti, A., & Pandolfi, P. P. (2011) · Nature Reviews Cancer · doi:10.1038/nrc3057 · Cited by 437 · see citing works
The power and the promise of oncogene-induced senescence markers
Collado, M., & Serrano, M. (2006) · Nature Reviews Cancer · doi:10.1038/nrc1884 · Cited by 404 · see citing works
Rakhra, K., Bachireddy, P., Zabuawala, T., Zeiser, R., Xu, L., Kopelman, A., Fan, A. C., Yang, Q., Braunstein, L., Crosby, E., et al. (2010) · Cancer Cell · doi:10.1016/j.ccr.2010.10.002 · Cited by 339 · see citing works
Telomere Length Abnormalities Occur Early in the Initiation of Epithelial Carcinogenesis
Meeker, A. K., Hicks, J. L., Iacobuzio-Donahue, C. A., Montgomery, E. A., Westra, W. H., Chan, T. Y., Ronnett, B. M., & De Marzo, A. M. (2004) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-0984-03 · Cited by 306 · see citing works
Coppé, J.-P., Patil, C. K., Rodier, F., Sun, Y., Muñoz, D. P., Goldstein, J., Nelson, P. S., Desprez, P.-Y., & Campisi, J. (2008) · PLoS Biology · doi:10.1371/journal.pbio.0060301 · Cited by 302 · cited 11× · see citing works
“Heatmap colors indicate the bols are color-coded to indicate genes designated as SIR genes (red), SASP re (Acosta et al., 2008; Coppé et al., 2008; Kuilman et al., 2008; Kuilman and ted genes that showed at least 2-fold upregulation averaged in both conditions olated fromCKIaKOmice at different…”
BackgroundMethodResultInfluentialCKIα ablation highlights a critical role for p53 in invasiveness control
Elyada, E., Pribluda, A., Goldstein, R. E., Morgenstern, Y., Brachya, G., Cojocaru, G., Snir-Alkalay, I., Burstain, I., Haffner‐Krausz, R., Jung, S., et al. (2011) · Nature · doi:10.1038/nature09673 · Cited by 199 · see citing works
Self-citationVarfolomeev, E. E., Goncharov, T., Maecker, H. L., Zobel, K., Kömüves, L. G., Deshayes, K., & Vucic, D. (2012) · Science Signaling · doi:10.1126/scisignal.2001878 · Cited by 194 · see citing works
Self-citationPetrova, T. V., Nykänen, A. I., Norrmén, C., Ivanov, K. I., Andersson, L. C., Haglund, C. H., Puolakkainen, P. A., Wempe, F., von Melchner, H., Gradwohl, G., et al. (2008) · Cancer Cell · doi:10.1016/j.ccr.2008.02.020 · Cited by 193 · see citing works
Self-citationTumor Stroma-Derived TGF-β Limits Myc-Driven Lymphomagenesis via Suv39h1-Dependent Senescence
Reimann, M., Lee, S., Loddenkemper, C., Dörr, J. R., Tabor, V., Aichele, P., Stein, H., Dörken, B., Jenuwein, T., & Schmitt, C. A. (2010) · Cancer Cell · doi:10.1016/j.ccr.2009.12.043 · Cited by 184 · see citing works
SHORT COMMUNICATION: Sulindac suppresses tumorigenesis in the Min mouse
Beazer-barclay, Y. D., Levy, D. B., Moser, A. R., Dove, W. F., Hamilton, S. R., Vogelstein, B., & Kinzler, K. W. (1996) · Carcinogenesis · doi:10.1093/carcin/17.8.1757 · Cited by 173 · see citing works
Sutherland, R. M., Buchegger, F., Schreyer, M., Vacca, A., & Mach, J. (1987) · PubMed · Cited by 151 · see citing works
Bartholomew, J. N., Volonté, D., & Galbiati, F. (2009) · Cancer Research · doi:10.1158/0008-5472.can-08-2857 · Cited by 106 · see citing works
Squires, D. F. (1965) · Science · doi:10.1126/science.148.3669.503 · Cited by 73 · see citing works
Ishikawa, T., & Herschman, H. R. (2010) · Carcinogenesis · doi:10.1093/carcin/bgq002 · Cited by 71 · see citing works
Cellular senescence bypass screen identifies new putative tumor suppressor genes
Martínez-Leal, J. F., Fominaya, J. M., Cascón, A., Guijarro, M. V., Blanco‐Aparicio, C., LLeonart, M. E., Castro, M. E., y Cajal, S. R., Robledo, M., Beach, D., et al. (2007) · Oncogene · doi:10.1038/sj.onc.1210846 · Cited by 64 · see citing works
Kim, B. H., Roh, E., Lee, H. Y., Lee, I.-J., Ahn, B., Jung, S., Lee, H., Han, S., & Kim, Y. S. (2008) · Molecular Pharmacology · doi:10.1124/mol.107.041251 · Cited by 62 · see citing works
Cytokine loops driving senescence
Bártek, J., Hodný, Z., & Lukas, J. (2008) · Nature Cell Biology · doi:10.1038/ncb0808-887 · Cited by 60 · see citing works
Fluorescence-Based Detection and Quantification of Features of Cellular Senescence
Cho, S., & Hwang, E. S. (2011) · Methods in cell biology · doi:10.1016/b978-0-12-385493-3.00007-3 · Cited by 50 · see citing works
Bhatia, B., Multani, A. S., Patrawala, L., Chen, X., Calhoun‐Davis, T., Zhou, J., Schroeder, L., Schneider‐Broussard, R., Shen, J., Pathak, S., et al. (2008) · International Journal of Cancer · doi:10.1002/ijc.23222 · Cited by 47 · see citing works
Fijneman, R. J. A., Bade, L. K., Peham, J. R., van de Wiel, M. A., van Hinsbergh, V. W. M., Meijer, G. A., O'Sullivan, M. G., & Cormier, R. T. (2009) · Analytical Cellular Pathology · doi:10.1155/2009/234121 · Cited by 36 · see citing works
Flagged first, then by citations
1 of the 56 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Inflammation and cancer: triggers, mechanisms, and consequences
Greten, F. R., & Grivennikov, S. I. (2019) · Immunity · doi:10.1016/j.immuni.2019.06.025 · Cited by 3,806 · see citing works
Inflammation-induced cancer: Crosstalk between tumours, immune cells and microorganisms
Elinav, E., Nowarski, R., Thaiss, C. A., Hu, B., Jin, C., & Flavell, R. A. (2013) · Nature reviews. Cancer · doi:10.1038/nrc3611 · Cited by 2,000 · see citing works
Exploiting senescence for the treatment of cancer
Wang, L., Lankhorst, L., & Bernards, R. (2022) · Nature Reviews Cancer · doi:10.1038/s41568-022-00450-9 · Cited by 867 · see citing works
Exosomes maintain cellular homeostasis by excreting harmful DNA from cells
Takahashi, A., Okada, R., Nagao, K., Kawamata, Y., Hanyu, A., Yoshimoto, S., Takasugi, M., Watanabe, S., Kanemaki, M. T., Obuse, C., et al. (2017) · Nature Communications · doi:10.1038/ncomms15287 · Cited by 761 · see citing works
The dynamic nature of senescence in cancer
Lee, S., & Schmitt, C. A. (2019) · Nature Cell Biology · doi:10.1038/s41556-018-0249-2 · Cited by 588 · see citing works
The senescence-associated secretory phenotype and its regulation
Lopes-Paciencia, S., Saint-Germain, E., Rowell, M.-C., Ruiz, A. F., Kalegari, P., & Ferbeyre, G. (2019) · Cytokine · doi:10.1016/j.cyto.2019.01.013 · Cited by 601 · see citing works
Cancer-Cell-Intrinsic Mechanisms Shaping the Tumor Immune Landscape
Wellenstein, M. D., & de Visser, K. E. (2018) · Immunity · doi:10.1016/j.immuni.2018.03.004 · Cited by 581 · see citing works
Genetic and biological hallmarks of colorectal cancerPreprint
Li, J., Ma, X., Chakravarti, D., Shalapour, S., & DePinho, R. A. (2021) · Genes & Development · doi:10.1101/gad.348226.120 · Cited by 588 · see citing works
Recent Developments in Radiotherapy
Citrin, D. E. (2017) · New England Journal of Medicine · doi:10.1056/nejmra1608986 · Cited by 496 · see citing works
Inflammatory networks underlying colorectal cancer
Lasry, A., Zinger, A., & Ben‐Neriah, Y. (2016) · Nature Immunology · doi:10.1038/ni.3384 · Cited by 488 · 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
Inside and out: the activities of senescence in cancer
Pérez-Mancera, P. A., Young, A. R. J., & Narita, M. (2014) · Nature Reviews Cancer · doi:10.1038/nrc3773 · Cited by 462 · see citing works
Jackstadt, R., van Hooff, S. R., Leach, J. D. G., Cortés-Lavaud, X., Lohuis, J. O., Ridgway, R. A., Wouters, V. M., Roper, J., Kendall, T. J., Roxburgh, C. S. D., et al. (2019) · Cancer Cell · doi:10.1016/j.ccell.2019.08.003 · Cited by 428 · see citing works
Senescence-associated inflammatory responses: aging and cancer perspectives
Lasry, A., & Ben-Neriah, Y. (2015) · Trends in Immunology · doi:10.1016/j.it.2015.02.009 · Cited by 408 · see citing works
Self-citationEmerging cytokine networks in colorectal cancer
West, N. R., McCuaig, S., Franchini, F., & Powrie, F. M. (2015) · Nature reviews. Immunology · doi:10.1038/nri3896 · Cited by 401 · see citing works
The gut microbiome switches mutant p53 from tumour-suppressive to oncogenic
Kadosh, E., Snir-Alkalay, I., Venkatachalam, A., May, S., Lasry, A., Elyada, E., Zinger, A., Shaham, M., Vaalani, G., Mernberger, M., et al. (2020) · Nature · doi:10.1038/s41586-020-2541-0 · Cited by 378 · see citing works
Self-citationTakahashi, A., Loo, T. M., Okada, R., Kamachi, F., Watanabe, Y., Wakita, M., Watanabe, S., Kawamoto, S., Miyata, K., Barber, G. N., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-03555-8 · Cited by 350 · see citing works
Targeting cancer-promoting inflammation — have anti-inflammatory therapies come of age?
Hou, J., Karin, M., & Sun, B. (2021) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-020-00459-9 · Cited by 376 · see citing works
Tissue homeostasis and inflammation
Meizlish, M. L., Franklin, R. A., Zhou, X., & Medzhitov, R. (2021) · Annual Review of Immunology · doi:10.1146/annurev-immunol-061020-053734 · Cited by 364 · see citing works
Watanabe, S., Kawamoto, S., Ohtani, N., & Hara, E. (2017) · Cancer Science · doi:10.1111/cas.13184 · Cited by 321 · see citing works
Chemotherapy Induces Senescence-Like Resilient Cells Capable of Initiating AML Recurrence
Duy, C., Li, M., Teater, M., Meydan, C., Garrett-Bakelman, F. E., Lee, T. C., Chin, C. R., Durmaz, C., Kawabata, K. C., Dhimolea, E., et al. (2021) · Cancer Discovery · doi:10.1158/2159-8290.cd-20-1375 · Cited by 253 · see citing works
Physiological and pathological consequences of cellular senescence
Burton, D. G. A., & Krizhanovsky, V. (2014) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-014-1691-3 · Cited by 253 · see citing works
Ageing: from inflammation to cancer
Leonardi, G. C., Accardi, G., Monastero, R., Nicoletti, F., & Libra, M. (2018) · Immunity & Ageing · doi:10.1186/s12979-017-0112-5 · Cited by 241 · see citing works
“Moreover, the paracrine signalling operated through SASP has been demonstrated to induce senescence in surrounding cells therefore propagating this process throughout the tissue [39–41].”
BackgroundInfluentialBiological functions of casein kinase 1 isoforms and putative roles in tumorigenesis
Schittek, B., & Sinnberg, T. W. (2014) · Molecular Cancer · doi:10.1186/1476-4598-13-231 · Cited by 245 · see citing works
Senescent cells: SASPected drivers of age-related pathologies
Ovadya, Y., & Krizhanovsky, V. (2014) · Biogerontology · doi:10.1007/s10522-014-9529-9 · Cited by 232 · see citing works
SASP: Tumor Suppressor or Promoter? Yes!
Rao, S. G., & Jackson, J. G. (2016) · Trends in Cancer · doi:10.1016/j.trecan.2016.10.001 · Cited by 206 · see citing works
Role of sphingolipids in senescence: implication in aging and age-related diseases
Trayssac, M., Hannun, Y. A., & Obeid, L. M. (2018) · Journal of Clinical Investigation · doi:10.1172/jci97949 · Cited by 210 · see citing works
Mesenchymal Cells in Colon Cancer
Koliaraki, V., Pallangyo, C. K., Greten, F. R., & Kollias, G. A. (2017) · Gastroenterology · doi:10.1053/j.gastro.2016.11.049 · Cited by 196 · see citing works
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 198 · see citing works
Interplay between DNA repair and inflammation, and the link to cancer
Kidane, D., Chae, W. J., Czochor, J. R., Eckert, K. A., Glazer, P. M., Bothwell, A. L. M., & Sweasy, J. B. (2014) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.3109/10409238.2013.875514 · Cited by 186 · see citing works
Cellular senescence and the tumour microenvironment
Takasugi, M., Yoshida, Y., & Ohtani, N. (2022) · Molecular Oncology · doi:10.1002/1878-0261.13268 · Cited by 178 · see citing works
Caught in the cross fire: p53 in inflammation
Cooks, T., Harris, C. C., & Oren, M. (2014) · Carcinogenesis · doi:10.1093/carcin/bgu134 · Cited by 160 · see citing works
Self-citationYu, Y., Schleich, K., Yue, B., Ji, S., Lohneis, P., Kemper, K., Silvis, M. R., Qutob, N., van Rooijen, E., Werner-Klein, M., et al. (2018) · Cancer Cell · doi:10.1016/j.ccell.2018.01.002 · Cited by 156 · see citing works
Exploring the multiple roles of guardian of the genome: P53
Feroz, W., & Sheikh, A. M. A. (2020) · Egyptian Journal of Medical Human Genetics · doi:10.1186/s43042-020-00089-x · Cited by 161 · see citing works
Minzel, W., Venkatachalam, A., Fink, A., Hung, E., Brachya, G., Burstain, I., Shaham, M., Rivlin, A., Omer, I., Zinger, A., et al. (2018) · Cell · doi:10.1016/j.cell.2018.07.045 · Cited by 155 · see citing works
Self-citationThe role of cellular senescence and SASP in tumour microenvironment
Takasugi, M., Yoshida, Y., Hara, E., & Ohtani, N. (2023) · The FEBS Journal · doi:10.1111/febs.16381 · Cited by 144 · see citing works
CK1α suppresses lung tumour growth by stabilizing PTEN and inducing autophagy
Cai, J., Li, R., Xu, X., Zhang, L., Lian, R., Fang, L., Huang, Y., Feng, X., Liu, X., Xu, L., et al. (2018) · Nature Cell Biology · doi:10.1038/s41556-018-0065-8 · Cited by 145 · see citing works
Pateras, I. S., Havaki, S., Nikitopoulou, X., Vougas, K. N., Townsend, P. A., Panayiotidis, M. I., Georgakilas, A. G., & Gorgoulis, V. G. (2015) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2015.06.011 · Cited by 143 · see citing works
The mechanical microenvironment in cancer: How physics affects tumours
Nagelkerke, A., Bussink, J., Rowan, A. E., & Span, P. N. (2015) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2015.09.001 · Cited by 158 · 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
Cancer and Aging - the Inflammatory Connection
Zinger, A., Cho, W. C. S., & Ben‐Yehuda, A. (2017) · Aging and Disease · doi:10.14336/ad.2016.1230 · Cited by 137 · see citing works
Cell spheroids: the new frontiers in in vitro models for cancer drug validation
Chatzinikolaidou, Μ. (2016) · Drug Discovery Today · doi:10.1016/j.drudis.2016.06.024 · Cited by 129 · see citing works
Casein kinase 1α: biological mechanisms and theranostic potential
Jiang, S., Zhang, M., Sun, J., & Yang, X. (2018) · Cell Communication and Signaling · doi:10.1186/s12964-018-0236-z · Cited by 130 · see citing works
Chemokines, cytokines and exosomes help tumors to shape inflammatory microenvironment
Атретханы, К.-С. Н., Drutskaya, M. S., Nedospasov, S. A., Grivennikov, S. I., & Kuprash, D. V. (2016) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2016.09.011 · Cited by 126 · see citing works
p53 and the Carcinogenicity of Chronic InflammationPreprint
Gudkov, A. V., & Komarova, E. A. (2016) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a026161 · Cited by 122 · see citing works
The Paradoxical Role of Cellular Senescence in Cancer
Yang, J., Liu, M., Hong, D., Zeng, M., & Zhang, X. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.722205 · Cited by 115 · see citing works
Are there roles for brain cell senescence in aging and neurodegenerative disorders?
Tan, F. C. C., Hutchison, E. R., Eitan, E., & Mattson, M. P. (2014) · Biogerontology · doi:10.1007/s10522-014-9532-1 · Cited by 116 · see citing works
Lunyak, V. V., Amaro-Ortiz, A., & Gaur, M. (2017) · Frontiers in Genetics · doi:10.3389/fgene.2017.00220 · Cited by 114 · see citing works
Simvastatin suppresses breast cancer cell proliferation induced by senescent cells
Liu, S., Uppal, H., Demaria, M., Desprez, P.-Y., Campisi, J., & Kapahi, P. (2015) · Scientific Reports · doi:10.1038/srep17895 · Cited by 124 · see citing works
Widespread parainflammation in human cancer
Aran, D., Lasry, A., Zinger, A., Biton, M., Pikarsky, E., Hellman, A., Butte, A. J., & Ben‐Neriah, Y. (2016) · Genome biology · doi:10.1186/s13059-016-0995-z · Cited by 104 · see citing works
Self-citationLineage Plasticity in Cancer Progression and Treatment
Magnen, C. L., Shen, M. M., & Abate-Shen, C. T. (2017) · Annual Review of Cancer Biology · doi:10.1146/annurev-cancerbio-030617-050224 · Cited by 105 · see citing works
Preoperative inflammatory markers of NLR and PLR as indicators of poor prognosis in resectable HCC
Wang, D., Bai, N., Hu, X., Ouyang, X., Yao, L., Tao, Y., & Wang, Z. (2019) · PeerJ · doi:10.7717/peerj.7132 · Cited by 105 · see citing works
Cellular senescence and tumor promotion: Is aging the key?
Loaiza, N., & Demaria, M. (2016) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2016.01.007 · Cited by 101 · see citing works
Inflammation fires up cancer metastasis
Qian, B. (2017) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2017.08.006 · Cited by 98 · see citing works
Cellular senescence in gastrointestinal diseases: from pathogenesis to therapeutics
Frey, N., Venturelli, S., Zender, L., & Bitzer, M. (2018) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2017.146 · Cited by 97 · see citing works
Cancer secretome and inflammation: The bright and the dark sides of NF-κB
Capece, D., Verzella, D., Tessitore, A., Alesse, E., Capalbo, C., & Zazzeroni, F. (2017) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2017.08.004 · Cited by 90 · see citing works
Opportunities for organoids as new models of aging
Hu, J. L., Todhunter, M. E., LaBarge, M. A., & Gartner, Z. J. (2017) · The Journal of Cell Biology · doi:10.1083/jcb.201709054 · Cited by 88 · see citing works
mTOR Activity and Autophagy in Senescent Cells, a Complex Partnership
Cayo, Á., Segovia, R., Venturini, W., Moore‐Carrasco, R., Valenzuela, C. A., & Brown, N. E. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22158149 · Cited by 92 · see citing works
Nakamura, M., Ohsawa, S., & Igaki, T. (2014) · Nature Communications · doi:10.1038/ncomms6264 · Cited by 79 · see citing works
Myeloid-derived suppressor cells (MDSC): an important partner in cellular/tissue senescence
Salminen, A., Kauppinen, A., & Kaarniranta, K. (2018) · Biogerontology · doi:10.1007/s10522-018-9762-8 · Cited by 84 · see citing works
Wu, Z., Uhl, B., Gires, O., & Reichel, C. A. (2023) · Journal of Biomedical Science · doi:10.1186/s12929-023-00915-5 · Cited by 78 · see citing works
The senescence journey in cancer immunoediting
Zingoni, A., Antonangeli, F., Sozzani, S., Santoni, A., Cippitelli, M., & Soriani, A. (2024) · Molecular Cancer · doi:10.1186/s12943-024-01973-5 · Cited by 74 · see citing works
Obesity and Cancer: A Gut Microbial Connection
Ohtani, N., Yoshimoto, S., & Hara, E. (2014) · Cancer Research · doi:10.1158/0008-5472.can-13-3501 · Cited by 70 · see citing works
Yanagi, S., Tsubouchi, H., Miura, A., Matsuo, A., Matsumoto, N., & Nakazato, M. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18030503 · Cited by 69 · see citing works
The Fire within: Cell-Autonomous Mechanisms in Inflammation-Driven Cancer
Todoric, J., & Karin, M. (2019) · Cancer Cell · doi:10.1016/j.ccell.2019.04.001 · Cited by 68 · see citing works
Chaudhary, P., Milluzzo, G., Ahmed, H., Odlozilik, B., McMurray, A., Prise, K. M., & Borghesi, M. (2021) · Frontiers in Physics · doi:10.3389/fphy.2021.624963 · Cited by 67 · see citing works
p53’s Extended Reach: The Mutant p53 Secretome
Pavlakis, E., & Stiewe, T. (2020) · Biomolecules · doi:10.3390/biom10020307 · Cited by 65 · see citing works
Self-citationZhao, B., Wu, B. C., Feng, N., Zhang, X., Zhang, X., Wei, Y., & Zhang, W. (2023) · Journal of Hematology & Oncology · doi:10.1186/s13045-023-01426-4 · Cited by 65 · see citing works
Two-signal requirement for growth-promoting function of Yap in hepatocytes
Su, T., Bondar, T., Zhou, X., Zhang, C., He, H., & Medzhitov, R. (2015) · eLife · doi:10.7554/elife.02948 · Cited by 64 · see citing works
Mitochondrial Dysfunction Meets Senescence
Gallage, S., & Gil, J. (2016) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2016.01.005 · Cited by 61 · see citing works
Senescence and cancer: An evolving inflammatory paradox
Ruhland, M. K., Coussens, L. M., & Stewart, S. A. (2015) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2015.10.001 · Cited by 60 · see citing works
Prodding the Beast: Assessing the Impact of Treatment-Induced Metastasis
Ebos, J. M. L. (2015) · Cancer Research · doi:10.1158/0008-5472.can-15-0308 · Cited by 59 · see citing works
p53 Isoforms in Cellular Senescence- and Ageing-Associated Biological and Physiological Functions
Fujita, K. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20236023 · Cited by 57 · see citing works
Prognostic implications of Aquaporin 9 expression in clear cell renal cell carcinoma
Xu, W., Shi, S.-N., Xu, Y., Wang, J., Wang, H., Cao, D., Shi, G., Qu, Y.-Y., Zhang, H.-L., & Ye, D. (2019) · Journal of Translational Medicine · doi:10.1186/s12967-019-2113-y · Cited by 53 · see citing works
Brandt, M., Grazioso, T. P., Fawal, M.-A., Tummala, K. S., Torres-Ruiz, R., Rodríguez, S., Perna, C., & Djouder, N. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.11.006 · Cited by 53 · see citing works
HMG-CoA Reductase Inhibition Delays DNA Repair and Promotes Senescence After Tumor Irradiation
Efimova, E. V., Ricco, N., Labay, E., Mauceri, H. J., Flor, A. C., Ramamurthy, A., Sutton, H. G., Weichselbaum, R. R., & Kron, S. J. (2017) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-17-0288 · Cited by 52 · see citing works
Ohtani, N. (2019) · The Journal of Biochemistry · doi:10.1093/jb/mvz055 · Cited by 52 · see citing works
The origins of tumor-promoting inflammation
Bondar, T., & Medzhitov, R. (2013) · Cancer Cell · doi:10.1016/j.ccr.2013.07.016 · Cited by 47 · see citing works
Fuentes-Fayos, A. C., G-García, M. E., Pérez‐Gómez, J. M., Montero‐Hidalgo, A. J., Martin-Colom, J., Rosa, C. D., Blanco-Acevedo, C., Torres, E., Toledano-Delgado, Á., Sánchez‐Sánchez, R., et al. (2023) · EBioMedicine · doi:10.1016/j.ebiom.2023.104484 · Cited by 47 · see citing works
Type I Interferons Control Proliferation and Function of the Intestinal Epithelium
Katlinskaya, Y. V., Katlinski, K. V., Lasri, A., Li, N., Beiting, D. P., Durham, A. C., Yang, T., Pikarsky, E., Lengner, C. J., Johnson, F. B., et al. (2016) · Molecular and Cellular Biology · doi:10.1128/mcb.00988-15 · Cited by 44 · see citing works
Self-citationMechanisms of hematopoietic clonal dominance in VEXAS syndrome
Molteni, R., Fiumara, M., Campochiaro, C., Alfieri, R. R., Pacini, G., Licari, E., Tomelleri, A., Diral, E., Varesi, A., Weber, A., et al. (2025) · Nature Medicine · doi:10.1038/s41591-025-03623-9 · Cited by 46 · see citing works
Chu, L., Qu, Y.-X., An, Y., Hou, L., Li, J., Li, W., Fan, G., Song, B., Li, E., Zhang, L., et al. (2022) · Cell Death and Disease · doi:10.1038/s41419-022-04601-6 · Cited by 45 · see citing works
Gemcitabine induces cell senescence in human pancreatic cancer cell lines
Song, Y. H., Baba, T., & Mukaida, N. (2016) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2016.06.063 · Cited by 42 · see citing works
Extracellular vesicles transmit epithelial growth factor activity in the intestinal stem cell niche
Oszvald, Á., Szvicsek, Z., Sándor, G. O., Kelemen, A., Soós, A. Á., Pálóczi, K., Bursics, A., Dede, K., Tölgyes, T., Buzás, E. I., et al. (2019) · Stem Cells · doi:10.1002/stem.3113 · Cited by 42 · see citing works
Self-citationZhang, K., Anumanthan, G., Scheaffer, S., & Cornelius, L. A. (2019) · Journal of Investigative Dermatology · doi:10.1016/j.jid.2018.05.035 · Cited by 39 · see citing works
Manni, S., Carrino, M., & Piazza, F. (2017) · Journal of Hematology & Oncology · doi:10.1186/s13045-017-0529-5 · Cited by 39 · see citing works
Gleason, C. E., Dickson, M. A., Klein, M. E., Antonescu, C. R., Gularte‐Mérida, R., Benitez, M., Delgado, J. I., Kataru, R. P., Tan, M. W. Y., Bradić, M., et al. (2023) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-23-2378 · Cited by 38 · see citing works
The radiobiology of laser-driven particle beams: focus on sub-lethal responses of normal human cells
Manti, L., Perozziello, F. M., Borghesi, M., Candiano, G., Chaudhary, P., Cirrone, G. A. P., Doria, D., Gwynne, D., Leanza, R., Prise, K. M., et al. (2017) · Journal of Instrumentation · doi:10.1088/1748-0221/12/03/c03084 · Cited by 38 · see citing works
Cellular senescence signaling in cancer: A novel therapeutic target to combat human malignancies
Fakhri, S., Moradi, S. Z., DeLiberto, L. K., & Bishayee, A. (2022) · Biochemical Pharmacology · doi:10.1016/j.bcp.2022.114989 · Cited by 38 · see citing works
Cellular senescence as a therapeutic target to improve renal transplantation outcome
van Willigenburg, H., de Keizer, P. L. J., & de Bruin, R. W. F. (2018) · Pharmacological Research · doi:10.1016/j.phrs.2018.02.015 · Cited by 38 · see citing works
Emerging Roles of Vitamin B12 in Aging and Inflammation
Simonenko, S. Y., Bogdanova, D. A., & Kuldyushev, N. A. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25095044 · Cited by 39 · see citing works
Kim, S. B., Bozeman, R., Kaisani, A. A., Kim, W., Zhang, L., Richardson, J. A., Wright, W. E., & Shay, J. W. (2015) · Oncogene · doi:10.1038/onc.2015.395 · Cited by 37 · see citing works
Dong, Q., Gao, H., Shi, Y., Zhang, F., Gu, X., Wu, A., Wang, D., Chen, Y., Bandyopadhyay, A., Yeh, I.-T., et al. (2016) · Aging · doi:10.18632/aging.101082 · Cited by 29 · see citing works
Manni, S., Carrino, M., Manzoni, M., Gianesin, K., Nunes, S. C., Costacurta, M., Tubi, L. Q., Macaccaro, P., Taìana, E., Cabrelle, A., et al. (2017) · Oncotarget · doi:10.18632/oncotarget.14654 · Cited by 36 · see citing works
CK1α ablation in keratinocytes induces p53-dependent, sunburn-protective skin hyperpigmentation
Chang, C., Kuo, C.-J., Ito, T., Su, Y.-Y., Jiang, S., Chiu, M., Lin, Y., Nist, A., Mernberger, M., Stiewe, T., et al. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1702763114 · Cited by 35 · see citing works
Self-citationPARP1 at the crossroad of cellular senescence and nucleolar processes
Kołacz-Milewska, K., & Robaszkiewicz, A. (2024) · Ageing Research Reviews · doi:10.1016/j.arr.2024.102206 · Cited by 34 · see citing works
Colorectal cancer initiation: Understanding early-stage disease for intervention
Jiang, C., Zhou, Q., Yi, K., Yuan, Y., & Xie, X. (2024) · Cancer Letters · doi:10.1016/j.canlet.2024.216831 · Cited by 34 · see citing works
Senescence-Inflammatory Regulation of Reparative Cellular Reprogramming in Aging and Cancer
Menéndez, J. A., & Alarcón, T. (2017) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2017.00049 · Cited by 32 · see citing works
Cho, W., Jin, X., Pang, J., Wang, Y., Mivechi, N. F., & Moskophidis, D. (2019) · Molecular and Cellular Biology · doi:10.1128/mcb.00391-18 · Cited by 33 · see citing works
Therapy-induced microenvironmental changes in cancer
Ma, Y., Yang, H., Pitt, J. M., Kroemer, G., & Zitvogel, L. (2016) · Journal of Molecular Medicine · doi:10.1007/s00109-016-1401-8 · Cited by 32 · see citing works
- Authors
- Pribluda, A., Elyada, E., Wiener, Z., Hamza, H., Goldstein, R. E., Biton, M., Burstain, I., Morgenstern, Y., Brachya, G., Billauer, H., Biton, S., Snir-Alkalay, I., Vucic, D., Schlereth, K., Mernberger, M., Stiewe, T., Oren, M., Alitalo, K., Pikarsky, E., & Ben-Neriah, Y.
- Affiliations
- Hebrew University of Jerusalem (IL)
- Genentech (US)
- Philipps University of Marburg (DE)
- Weizmann Institute of Science (IL)
- University of Helsinki (FI)
- Corresponding author
- Pikarsky, Eli
- ORCID
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2013-08
- Volume
- 24
- Issue
- 2
- Pages
- 242-256
- ISSN
- 1535-6108 (ISSN-L)
- OpenAlex
- W1981033124
- Cited by
- 239
- References
- 56
- Citations by year
- 2026: 8 · 2025: 17 · 2024: 22 · 2023: 20 · 2022: 20 · 2021: 20 · 2020: 13 · 2019: 20 · 2018: 18 · 2017: 26 · 2016: 23 · 2015: 15 · 2014: 14 · 2013: 3
- FWCI
- 12.69
- Type
- journal article
- Language
- en
- Update notices
- erratum (2015-06-08)
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cancer Cell (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- cellular senescence, p53, CSNK1A1, colorectal cancer, intestinal organoids, carcinogenesis, tumor invasion, nonsteroidal anti-inflammatory drugs, anti-inflammatory therapy
- MeSH terms
- Animals, Anti-Inflammatory Agents, Non-Steroidal, Cell Transformation, Neoplastic, Inflammation, Neoplasms, Cellular Senescence, Mice, Knockout, 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