Senescence in tumours: evidence from mice and humans
Open accessAbstract
The importance of cellular senescence, which is a stress response that stably blocks proliferation, is increasingly being recognized. Senescence is prevalent in pre-malignant tumours, and progression to malignancy requires evading senescence. Malignant tumours, however, may still undergo senescence owing to interventions that restore tumour suppressor function or inactivate oncogenes. Senescent tumour cells can be cleared by immune cells, which may result in efficient tumour regression. Standard chemotherapy also has the potential to induce senescence, which may partly underlie its therapeutic activity. Although these concepts are well supported in mouse models, translating them to clinical oncology remains a challenge.
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There is little doubt that the senescence growth arrest suppresses the development of cancer.
“There is little doubt that the senescence growth arrest suppresses the development of cancer (8, 48, 136).”
From Aging, Cellular Senescence, and Cancer (2013) · cites this paper as [136]
Other senescence markers are overexpressed or activated in cancer.
“Other senescence markers have been shown to be overexpressed or activated in cancer152.”
From Guidelines for minimal information on cellular senescence experimentation in vivo (2024) · cites this paper as [152]
Cellular senescence restrains cancer by imposing a cell-autonomous block to proliferation of oncogenically damaged/stressed cells.
“Whatever the case, the examples above, and a growing list of similar studies (Collado and Serrano, 2010), argue that cellular senescence restrains cancer by imposing a cell-autonomous block to the proliferation of oncogenically damaged/stressed cells (Fig. 2).”
From Four faces of cellular senescence (2011) · cites this paper as Collado and Serrano, 2010
A SASP profile can be determined by activation of molecular cascades linked to p53/p21 due to persistent double strand breaks or telomere shortening.
“A SASP profile can be further determined by the activation of molecular cascades linked to p53/p21 (due to persistent double strands breaks/telomere shortening)”
From The Role of Antioxidants in the Interplay between Oxidative Stress and Senescence (2022) · cites this paper as [24]
A SASP profile can be determined by activation of p16/Rb due to epigenetic modifications.
“but also to p16/Rb (due to epigenetic modifications) [3,22,24,25,26]”
From The Role of Antioxidants in the Interplay between Oxidative Stress and Senescence (2022) · cites this paper as [24]
Senescence is a key mechanism by which p53 suppresses tumorigenesis.
“It is believed that senescence is a key mechanism by which p53 suppresses tumorigenesis (Braig and Schmitt, 2006; Collado and Serrano, 2010).”
From p53-dependent chemokine production by senescent tumor cells supports NKG2D-dependent tumor elimination by natural killer cells (2013) · cites this paper as Collado and Serrano, 2010
Senescence escape is required for tumor progression to overt malignancy.
“Therefore, it has been proposed that senescence escape is required for tumor progression to overt malignancy [18,21].”
From Mechanisms and Regulation of Cellular Senescence (2021) · cites this paper as [21]
Senescence has also been implicated in promoting carcinogenesis and age-related pathologies through the senescence-associated secretory phenotype.
“However, senescence has also been implicated both in promoting carcinogenesis 15 and in age-related pathologies 16,17 through its autocrine and paracrine effects, known as the senescence-associated secretory phenotype (SASP) originally described by the Campisi group.18,19”
From Senescence from G2 arrest, revisited (2015) · cites this paper as [15]
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“Cellular senescence is another p53-dependent program that limits tumorigenesis (Collado and Serrano, 2010).”
BackgroundT-helper-1-cell cytokines drive cancer into senescence
Braumüller, H., Wieder, T., Brenner, E., Aßmann, S., Hahn, M., Alkhaled, M., Schilbach, K., Essmann, F., Kneilling, M., Griessinger, C., et al. (2013) · Nature · doi:10.1038/nature11824 · Cited by 720 · see citing works
Radiation-induced cell death mechanisms
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“However, also molecules involved in the DNA damage response (DDR) as well as novel markers obtained from microarray studies have been used as surrogate markers of this process [ 121 ].”
MethodRole of p53 in the Regulation of Cellular Senescence
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“Cellular senescence is a physiological mechanism adopted by cells to limit tumorigenesis [99,100], and for this reason, a therapy-induced senescence was considered as an alternative and possibly safer approach to the traditional cancer therapy, which aimed at inducing extensive DNA damage [101].”
BackgroundA key role for mitochondrial gatekeeper pyruvate dehydrogenase in oncogene-induced senescence
Kaplon, J., Zheng, L., Meissl, K., Chaneton, B., Selivanov, V. A., Mackay, G., van der Burg, S. H., Verdegaal, E. M. E., Cascante, M., Shlomi, T., et al. (2013) · Nature · doi:10.1038/nature12154 · Cited by 633 · see citing works
Senescent cells as a source of inflammatory factors for tumor progression
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“Senescent cells are detected in culture and in vivo by a variety of markers, including the senescence-associated β-galactosidase (SAβgal) [28], p16 [39], telomere-associated DNA damage foci [40], senescence-associated heterochromatin foci [41], and several other molecules; all of these markers have some limitations, a…”
BackgroundThe dynamic nature of autophagy in cancerPreprint
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“There is a wealth of literature demonstrating the anti-proliferative effects of high levels of oncogenic Ras expression in primary cells as a barrier to transformation (Collado and Serrano 2010; Kuilman et al. 2010), and, perhaps in the initial stages of transformation, autophagy provides a barrier.”
BackgroundSynthetic lethal metabolic targeting of cellular senescence in cancer therapy
Dörr, J. R., Yu, Y., Milanovic, M., Beuster, G., Zasada, C., Däbritz, J. H. M., Lisec, J., Lenze, D., Gerhardt, A., Schleicher, K., et al. (2013) · Nature · doi:10.1038/nature12437 · Cited by 541 · see citing works
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“Cell staining and observation revealed enlarged cell morphology and significant expression of b-gal, a widely used marker of cancer cell senescence (48), in A549 cells 24 hours afterWZB117 treatment (Fig.”
BackgroundMitochondrial dysfunction and oxidative stress in aging and cancer
Kudryavtseva, A. V., Krasnov, G. S., Dmitriev, A. A., Alekseev, B. Y., Kardymon, O. L., Садритдинова, А. Ф., Fedorova, M., Pokrovsky, A. V., Melnikova, N. V., Каприн, А. Д., et al. (2016) · Oncotarget · doi:10.18632/oncotarget.9821 · Cited by 551 · see citing works
“In contrast to cancer cells, normal cells at the end of their replicative life span are in a process known as cellular senescence which is characterized by irreversible cell cycle arrest, morphological changes, epigenetic modifications, lack of response to growth factors, telomere shortening and dysfunction, sustained…”
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“The Senescence Program Present in Low-Grade mPanIN Is Abrogated during Progression to High-Grade mPanIN Lesions Metaplasias and low-grade mPanINs observed in mice expressing K-RasG12V since embryonic development display senescence markers similar to those present in preneoplastic stages of other tumor types (Collado a…”
BackgroundInfluentialSelf-citationThe DREAM complex: master coordinator of cell cycle-dependent gene expression
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EMT-activating transcription factors in cancer: beyond EMT and tumor invasiveness
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“Oncogene-induced senescence has been identified in precancerous lesions and needs to be overcome for progression to full tumorigenic status [232, 233].”
BackgroundThe quest to slow ageing through drug discovery
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“The importance of the SASP phenotype has also been recognized in vivo in a variety of pathophysiologic contexts, giving rise to not only deleterious effects such as chronic inflammation and tumorigenesis (4, 8, 9), but also beneficial effects such as embryonal development (10, 11), immunosurveillance (12–14), and tiss…”
BackgroundInflammation and Liver Cancer: Molecular Mechanisms and Therapeutic Targets
Yang, Y. M., Kim, S., & Seki, E. (2019) · Seminars in Liver Disease · doi:10.1055/s-0038-1676806 · Cited by 453 · see citing works
Pro-senescence therapy for cancer treatment
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BRD4 Connects Enhancer Remodeling to Senescence Immune Surveillance
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“For example, cellular senescence can restrict tumorigenesis (4, 5) and modulate chemotherapy responses (6–8), and may exert a primordial role in wound healing, tissue remodeling, and repair (9–13).”
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“2013 Vol. 210 No. 10 2057-2069 www.jem.org/cgi/doi/10.1084/jem.20130783 2057 Cellular senescence is an established cellular stress response, primarily acting to limit the pro liferative potential of cells (Collado and Serrano, 2010).”
InfluentialBiomarkers of cellular senescence and skin aging
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“As senescent cells are terminally growth arrested, cell cycle regulators such as p16INK4a, p21CIP1 and p53 (Collado and Serrano, 2010) are commonly employed to detect senescent cells.”
BackgroundIlié, M., Hofman, V., Long-Mira, É., Selva, É., Vignaud, J.-M., Padovani, B., Mouroux, J., Marquette, C., & Hofman, P. M. (2014) · PLoS ONE · doi:10.1371/journal.pone.0111597 · Cited by 413 · see citing works
“However, oncogenic KRAS has differing effects – in some cases, it induces hyperproliferation, whereas in others it leads to oncogene induced senescence [43].”
BackgroundMechanisms and Regulation of Cellular Senescence
Roger, L., Tomas, F., & Gire, V. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222313173 · Cited by 395 · see citing works
“Therefore, it has been proposed that senescence escape is required for tumor progression to overt malignancy [18,21].”
BackgroundA model for RAS mutation patterns in cancers: finding the sweet spot
Li, S., Balmain, A., & Counter, C. M. (2018) · Nature Reviews Cancer · doi:10.1038/s41568-018-0076-6 · Cited by 384 · see citing works
Recognition of Tumors by the Innate Immune System and Natural Killer Cells
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Tumour-infiltrating Gr-1+ myeloid cells antagonize senescence in cancer
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Self-citationInterplay between oncogene-induced DNA damage response and heterochromatin in senescence and cancer
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The Biology of Aging and Cancer: A Brief Overview of Shared and Divergent Molecular Hallmarks
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Cellular senescence: putting the paradoxes in perspective
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“There are now numerous examples of the senescence response acting to suppress cancer progression in both mice and humans [38].”
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Guidelines for minimal information on cellular senescence experimentation in vivo
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Self-citationA versatile drug delivery system targeting senescent cells
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“…of inflammatory cells, the dismissal of senescent cells by phagocytic and immune cells, and the activation of stem/progenitor features in non-damaged surrounding cells (Krizhanovsky et al, 2008; Demaria et al, 2014; Yun et al, 2015; Mosteiro et al, 2016; Chiche et al, 2017; Ritschka et al, 2017).”
BackgroundSelf-citationWatanabe, S., Kawamoto, S., Ohtani, N., & Hara, E. (2017) · Cancer Science · doi:10.1111/cas.13184 · Cited by 321 · see citing works
Senescence from G2 arrest, revisited
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“Oncogene-induced senescence is an important mechanism for protection from tumourigenesis in vivo and current research suggests that it may be possible to activate senescence-inducing pathways for cancer therapy (Collado and Serrano, 2010; Lin et al., 2010).”
BackgroundDYRK1A protein kinase promotes quiescence and senescence through DREAM complex assembly
Litovchick, L., Florens, L. A., Swanson, S. K., Washburn, M. P., & DeCaprio, J. A. (2011) · Genes & Development · doi:10.1101/gad.2034211 · Cited by 302 · see citing works
“Oncogene-induced senescence in premalignant lesions in mouse models as well as in some human tumors could serve as a protective tumor suppressor mechanism (for review, see Collado and Serrano 2010).”
BackgroundMetformin: Multi-faceted protection against cancer
Barco, S. D., Vázquez‐Martín, A., Cufí, S., Oliveras‐Ferraros, C., Bosch‐Barrera, J., Joven, J., Martı́n-Castillo, B., & Menéndez, J. A. (2011) · Oncotarget · doi:10.18632/oncotarget.387 · Cited by 302 · see citing works
“Studies of human cancer tissues and cancerprone mice argue strongly that cellular senescence is an important physiological mechanism in protecting cells against malignant transformation [154-156].”
BackgroundTargeting senescent cells in translational medicine
Pàez‐Ribes, M., González‐Gualda, E., Doherty, G. J., & Muñoz‐Espín, D. (2019) · EMBO Molecular Medicine · doi:10.15252/emmm.201810234 · Cited by 289 · see citing works
“A major consequence of senescence appears to prevent propagation of pre-malignant cells, providing a crucial barrier to tumorigenesis (Collado & Serrano, 2010).”
BackgroundCellular senescence and the aging brain
Chinta, S. J., Woods, G., Rane, A., Demaria, M., Campisi, J., & Andersen, J. K. (2015) · Experimental Gerontology · doi:10.1016/j.exger.2014.09.018 · Cited by 282 · see citing works
“The senescence response arrests cell proliferation , stably and essentially irreversibly, in response to stresses that puts cells at risk for malignant transformation (Campisi, 2001; Collado and Serrano, 2010; Prieri et al., 2008).”
Rho GTPase signaling in cancer progression and dissemination
Crosas‐Molist, E., Samain, R., Kohlhammer, L., Orgaz, J. L., George, S. L., Maiques, Ó., Barcelo, J., & Sanz‐Moreno, V. (2021) · Physiological Reviews · doi:10.1152/physrev.00045.2020 · Cited by 277 · see citing works
Cell fusion induced by ERVWE1 or measles virus causes cellular senescence
Chuprin, A., Gal, H., Biron-Shental, T., Biran, A., Amiel, A., Rozenblatt, S., & Krizhanovsky, V. (2013) · Genes & Development · doi:10.1101/gad.227512.113 · Cited by 262 · see citing works
“These triggers as well as others yet unidentified lead to senescent cell accumulation in aged tissues, premalignant lesions, tumors after therapy, and tissue damage (Dimri et al. 1995; Schmitt et al. 2002; Krizhanovsky et al. 2008; Collado and Serrano 2010; Jun and Lau 2010; Kuilman et al. 2010).”
BackgroundBird, 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 · see citing works
“They also express a suite of senescence markers (38), including markers of the DNA damage response, growth arrest and the SASP.”
Self-citationFarr, J. N., & Khosla, S. (2019) · Bone · doi:10.1016/j.bone.2019.01.015 · Cited by 263 · see citing works
“What is becoming clear, however, is that in addition to the wellestablished mechanism of tumor suppression to protect against unrestricted growth of damaged cells and prevent cancer [15, 16], senescent cells and their SASP have important roles in, for example, fine-tuning embryonic development [17, 18] and promoting t…”
BackgroundCharacterization of novel markers of senescence and their prognostic potential in cancer
Althubiti, M., Lezina, L., Carrera, S., Jukes-Jones, R., Giblett, S. M., Antonov, A., Barlev, N., Saldanha, G. S., Pritchard, C. A., Cain, K., et al. (2014) · Cell Death & Disease · doi:10.1038/cddis.2014.489 · Cited by 256 · see citing works
“Senescence is usually defined as a permanent cell cycle arrest in which cells remain metabolically active and adopt characteristic phenotypic changes.(2) Senescent cells often appear multinucleated, large and extended, and exhibit spindle and vacuolization features.”
BackgroundAbrogation of BRAFV600E-induced senescence by PI3K pathway activation contributes to melanomagenesisPreprint
Vredeveld, L. C. W., Possik, P. A., Smit, M. A., Meissl, K., Michaloglou, C., Horlings, H. M., Ajouaou, A., Kortman, P. C., Dankort, D. L., McMahon, M., et al. (2012) · Genes & Development · doi:10.1101/gad.187252.112 · Cited by 258 · see citing works
“The factors and pathways identified in this way will likely be relevant for other tumor settings as well, as OIS is seen in many tissue types (Collado and Serrano 2010).”
BackgroundGut bacteria identified in colorectal cancer patients promote tumourigenesis via butyrate secretion
Okumura, S., Konishi, Y., Narukawa, M., Sugiura, Y., Yoshimoto, S., Arai, Y., Sato, S., Yoshida, Y., Tsuji, S., Uemura, K., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-25965-x · Cited by 264 · see citing works
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“dtd" [ ]> Cellular senescence represents a robust and essentially irreversible tumour-suppressive barrier that cells must overcome to develop into a full-blown malignanc”
Cell Senescence: Role in Aging and Age-Related Diseases
Campisi, J., & Robert, L. (2014) · Interdisciplinary Topics in Gerontology and Geriatrics · doi:10.1159/000358899 · Cited by 240 · see citing works
Oncogene addiction: pathways of therapeutic response, resistance, and road maps toward a cure
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Clearance of senescent macrophages ameliorates tumorigenesis in KRAS-driven lung cancer
Haston, S., Gonzalez-Gualda, E., Morsli, S., Ge, J., Reen, V., Calderwood, A., Moutsopoulos, I., Panousopoulos, L., Deletic, P., Carreno, G., et al. (2023) · Cancer Cell · doi:10.1016/j.ccell.2023.05.004 · Cited by 251 · see citing works
“of damaged cells to proliferate.(13) Paradoxically, cellular senescence can also exert a variety of tumor-promoting effects, depending on the cellular context and composition of the SASP.”
BackgroundA Senescence-Inflammatory Switch from Cancer-Inhibitory to Cancer-Promoting Mechanism
Pribluda, A., Elyada, E., Wiener, Z., Hamza, H., Goldstein, R. E., Biton, M., Burstain, I., Morgenstern, Y., Brachya, G., Billauer, H., et al. (2013) · Cancer Cell · doi:10.1016/j.ccr.2013.06.005 · Cited by 239 · 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).”
BackgroundVendetti, F. P., Lau, A., Schamus, S., Conrads, T. P., O’Connor, M. J., & Bakkenist, C. J. (2015) · Oncotarget · doi:10.18632/oncotarget.6247 · Cited by 241 · see citing works
Senescence and Cancer: A Review of Clinical Implications of Senescence and Senotherapies
Wyld, L., Bellantuono, I., Tchkonia, T., Morgan, J., Turner, O., Foss, F., George, J., Danson, S., & Kirkland, J. L. (2020) · Cancers · doi:10.3390/cancers12082134 · Cited by 235 · see citing works
“Other mechanisms of tumour suppression have been proposed [35].”
BackgroundFibronectin in Cancer: Friend or Foe
Lin, T.-C., Yang, C.-H., Cheng, L.-H., Chang, W., Lin, Y.-R., & Cheng, H.-C. (2019) · Cells · doi:10.3390/cells9010027 · Cited by 235 · see citing works
Nuclear morphology is a deep learning biomarker of cellular senescence
Heckenbach, I., Mkrtchyan, G. V., Ezra, M. B., Bakula, D., Madsen, J. S., Nielsen, M. H., Oró, D., Osborne, B., Covarrubias, A. J., Idda, M. L., et al. (2022) · Nature Aging · doi:10.1038/s43587-022-00263-3 · Cited by 232 · see citing works
“Although oncogenic events are associated with the formation of senescent cells 17 , we speculate that individuals with higher propensity toward developing senescent cells have reduced formation of malignant neoplasm and are at lower risk of cancer.”
BackgroundWiel, C., Lallet-Daher, H., Gitenay, D., Gras, B., Le Calvé, B., Augert, A., Ferrand, M., Prevarskaya, N., Simonnet, H., Vindrieux, D., et al. (2014) · Nature Communications · doi:10.1038/ncomms4792 · Cited by 231 · see citing works
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Glucocorticoids suppress selected components of the senescence‐associated secretory phenotype
Laberge, R., Zhou, L., Sarantos, M. R., Rodier, F., Freund, A., de Keizer, P. L. J., Liu, S., Demaria, M., Cong, Y., Kapahi, P., et al. (2012) · Aging Cell · doi:10.1111/j.1474-9726.2012.00818.x · Cited by 229 · see citing works
“Cellular senescence is a potent tumor suppressive mechanism that arrests the proliferation, essentially irreversibly, of cells at risk for malignant transformation (Campisi, 2001; Collado & Serrano, 2010).”
BackgroundSuram, A., Kaplunov, J., Patel, P. L., Ruan, H., Cerutti, A., Boccardi, V., Fumagalli, M., Di Micco, R., Mirani, N., Gurung, R. L., et al. (2012) · The EMBO Journal · doi:10.1038/emboj.2012.132 · Cited by 227 · see citing works
“Studies conducted using mouse model systems suggest that cellular senescence arrests tumour growth before cells become malignant and invade surrounding tissue (Collado and Serrano, 2010).”
Karachaliou, N., Mayo, C., Costa, C., Magrí, I., Giménez-Capitán, A. A., Molina‐Vila, M. Á., & Rosell, R. (2012) · Clinical Lung Cancer · doi:10.1016/j.cllc.2012.09.007 · Cited by 232 · see citing works
miR-29 and miR-30 regulate B-Myb expression during cellular senescence
Martínez, I., Cazalla, D., Almstead, L. L., STEITZ, J. A., & DiMaio, D. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1017346108 · Cited by 221 · see citing works
“S is an important block to cell cycle progression during the aging of cells in culture and is a fundamental barrier that cells must bypass during carcinogenesis (1, 2).”
BackgroundCellular Differences in Protein Synthesis Regulate Tissue Homeostasis
Buszczak, M., Signer, R. A. J., & Morrison, S. J. (2014) · Cell · doi:10.1016/j.cell.2014.09.016 · Cited by 215 · see citing works
Immunosurveillance of senescent cells: the bright side of the senescence program
Sagiv, A., & Krizhanovsky, V. (2013) · Biogerontology · doi:10.1007/s10522-013-9473-0 · Cited by 208 · see citing works
“Since its initial discovery, DCR2 has been widely used, along with other biomarkers, to characterize senescent cells in premalignant lesions albeit its functional role to the senescence program has been unknown (Collado et al. 2005; Collado and Serrano 2010).”
BackgroundHerdy, J. R., Traxler, L., Agarwal, R. K., Karbacher, L., Schlachetzki, J. C. M., Boehnke, L., Zangwill, D., Galasko, D., Glass, C. K., Mertens, J., et al. (2022) · Cell Stem Cell · doi:10.1016/j.stem.2022.11.010 · Cited by 208 · see citing works
Barascu, A., Le Chalony, C., Pennarun, G., Genet, D., Imam, N., Lopez, B., & Bertrand, P. (2012) · The EMBO Journal · doi:10.1038/emboj.2011.492 · Cited by 206 · see citing works
“Consistently, senescence can be induced by replicative stress or oncogene expression (Collado and Serrano, 2010).”
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
Cartilage regeneration and ageing: Targeting cellular plasticity in osteoarthritis
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Self-citationIsoform-specific p73 knockout mice reveal a novel role for ΔNp73 in the DNA damage response pathwayPreprint
Wilhelm, M., Rufini, A., Wetzel, M. K., Tsuchihara, K., Inoue, S., Tomasini, R., Itie-YouTen, A., Wakeham, A. C., Arsenian‐Henriksson, M., Melino, G., et al. (2010) · Genes & Development · doi:10.1101/gad.1873910 · Cited by 203 · see citing works
“Indeed, activation of the p16–RB axes is known to play a role in the establishment of senescence in tumors and to act in parallel to or overlapping with the Arf–p53 axes (Campisi and d’Adda di Fagagna 2007; Collado and Serrano 2010).”
BackgroundHan, Y., & Kim, S. Y. (2023) · Experimental & Molecular Medicine · doi:10.1038/s12276-022-00906-w · Cited by 201 · see citing works
The two sides of chromosomal instability: drivers and brakes in cancer
Hosea, R., Hillary, S., Naqvi, S., Wu, S., & Kasim, V. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01767-7 · Cited by 205 · see citing works
“362,363 In addition, senescent cells could be further cleared through autophagic cell death.”
BackgroundFan, T., Jiang, S., Chung, N., Alikhan, A., Ni, C., Lee, C. R., & Hornyak, T. J. (2011) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-10-0511 · Cited by 192 · see citing works
“Since senescence is a distinct mechanism of tumor suppression (2, 15, 16), determining how melanoma cells escape senescence and devising methods to restore senescence to these cells may be important for developing additional therapeutic options for this malignancy.”
BackgroundCellular 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
Histone variant H2A.J accumulates in senescent cells and promotes inflammatory gene expression
Contrepois, K., Coudereau, C., Benayoun, B. A., Schuler, N., Roux, P.-F., Bischof, O., Courbeyrette, R., Carvalho, C., Thuret, J.-Y., Ma, Z., et al. (2017) · Nature Communications · doi:10.1038/ncomms14995 · Cited by 191 · see citing works
“Up-regulated genes were greatly enriched in GO terms related to inflammatory/immune/secreted proteins (35/50 top GO classes) as previously reported for senescent cells (Supplementary Data 2).”
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“The authors suggested that HSCs are deactivated in the healing liver [193].”
BackgroundMethodInfluentialHIF1α is required for survival maintenance of chronic myeloid leukemia stem cells
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Nuclear Morphometric Analysis (NMA): Screening of Senescence, Apoptosis and Nuclear Irregularities
Filippi‐Chiela, E. C., Oliveira, M. M., Jurkovski, B., Callegari-Jacques, S. M., da Silva, V. D., & Lenz, G. (2012) · PLoS ONE · doi:10.1371/journal.pone.0042522 · Cited by 191 · see citing works
“Both replicative senescence and oncogene-induced senescence are important anti-cancer mechanisms and reactivation of senescence by therapy may represent a good anticancer strategy [4,5].”
BackgroundOncogene-induced senescence: a double edged sword in cancer
Liu, X., Ding, J., & Meng, L. (2018) · Acta Pharmacologica Sinica · doi:10.1038/aps.2017.198 · Cited by 191 · see citing works
Assessing cell and organ senescence biomarkers
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- Authors
- Collado, M., & Serrano, M.
- Affiliations
- Spanish National Cancer Research Centre (ES)
- Venue
- Nature Reviews Cancer
- Published
- 2010-01
- Volume
- 10
- Issue
- 1
- Pages
- 51-57
- ISSN
- 1474-175X (ISSN-L)
- 1474-1768
- PMC
- PMC3672965
- OpenAlex
- W2087999409
- Cited by
- 1,124
- References
- 58
- Citations by year
- 2026: 34 · 2025: 40 · 2024: 56 · 2023: 73 · 2022: 60 · 2021: 64 · 2020: 47 · 2019: 67 · 2018: 66 · 2017: 66 · 2016: 73 · 2015: 81 · 2014: 104 · 2013: 102 · 2012: 82
- FWCI
- 6.97
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature reviews. Cancer (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion)
- 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 › Oncology › Cancer-related Molecular Pathways
- Keywords
- oncogene-induced senescence, cellular senescence, tumor suppressor function, tumor regression, chemotherapy-induced senescence, senescence therapy, mouse tumor model
- MeSH terms
- Animals, Disease Models, Animal, Humans, Neoplasms, Cellular Senescence, Mice
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