The DOI matches its Crossref record; 58 of the 58 references it cites were found in a registry or an index.
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The cited source says what the claim attributes to it.
In the citing paper
“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]
The cited source says what the claim attributes to it.
In the citing paper
“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]
The cited source says what the claim attributes to it.
In the citing paper
“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
In the citing paper
“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]
In the citing paper
“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]
In the citing paper
“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
In the citing paper
“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]
In the citing paper
“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]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
The serial cultivation of human diploid cell strains
Hayflick, L., & Moorhead, P. S. (1961) · Experimental Cell Research · doi:10.1016/0014-4827(61)90192-6 · Cited by 8,508
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
Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a
Serrano, M., Lin, A. W., McCurrach, M. E., Beach, D., & Lowe, S. W. (1997) · Cell · doi:10.1016/s0092-8674(00)81902-9 · Cited by 5,218 · cited 1×
“More than a decade ago, a phenotype similar to senescence was unexpectedly observed on overexpression of an oncogenic version of HRAS (HRAS G12V ) in normal cells grown in vitro”
BackgroundSelf-citationSenescence 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
Rb-mediated heterochromatin formation and silencing of E2F target genes during cellular senescence
Narita, M., Nuñez, S., Heard, E., Narita, M., Lin, A. W., Hearn, S. A., Spector, D. L., Hannon, G. J., & Lowe, S. W. (2003) · Cell · doi:10.1016/s0092-8674(03)00401-x · Cited by 2,278 · cited 1×
“This histone methyltransferase is involved in the formation of heterochromatin and could be relevant for the formation of senescence-associated heterochromatin foci (SAHF), which are domains of silenced chromatin considered important for the senescent phenotyp”
BackgroundBRAFE600-associated senescence-like cell cycle arrest of human naevi
Michaloglou, C., Vredeveld, L. C. W., Soengas, M. S., Denoyelle, C., Kuilman, T., van der Horst, C. M. A. M., Majoor, D. M., Shay, J. W., Mooi, W. J., & Peeper, D. S. (2005) · Nature · doi:10.1038/nature03890 · Cited by 2,160
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
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
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
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 · cited 1×
“Most of the sarcomas, lymphomas and liver carcinomas that developed in the absence of p53 regressed after p53 restoratio”
Background
Flagged first, then by citations
Research works printed but not linked: 1
- Morton, J. P. et al. Mutant but not knockout p53 drives metastatic pancreatic cancer. Proc. Natl Acad. Sci. USA (in the press).
Cited by
Sorted by citations
Items 101–200 of 1,000
Patterns of Early p21 Dynamics Determine Proliferation-Senescence Cell Fate after Chemotherapy
Hsu, C.-H., Altschuler, S. J., & Wu, L. F. (2019) · Cell · doi:10.1016/j.cell.2019.05.041 · Cited by 181
“Clinically, there is growing evidence that therapy-induced senescence occurs in tumors and is associated with improved clinical outcomes (Collado and Serrano, 2010; Haugstetter et al., 2010; Roninson, 2003; Schmitt et al., 2002).”
BackgroundBennecke, M., Kriegl, L., Bajbouj, M., Retzlaff, K., Robine, S., Jung, A., Arkan, M. C., Kirchner, T., & Greten, F. R. (2010) · Cancer Cell · doi:10.1016/j.ccr.2010.06.013 · Cited by 186
“Oncogene induced senescence has been suggested to have a tumor suppressive function in a variety of different tumors (Collado and Serrano, 2010).”
BackgroundFOXM1 (Forkhead box M1) in Tumorigenesis
Wierstra, I. (2013) · Advances in cancer research · doi:10.1016/b978-0-12-407190-2.00016-2 · Cited by 190
Anti-senescence compounds: A potential nutraceutical approach to healthy aging
Gurău, F., Baldoni, S., Prattichizzo, F., Espinosa, E., Amenta, F., Procopio, A. D., Albertini, M. C., Bonafè, M., & Olivieri, F. (2018) · Ageing Research Reviews · doi:10.1016/j.arr.2018.05.001 · Cited by 179
“However, senescence features are expressed in premalignant tumors, where progression to malignancy requires evading senescence (Collado and Serrano, 2010; Campisi and d’Adda di Fagagna, 2007).”
Han, Z., Wang, K., Ding, S., & Zhang, M. (2024) · Bone Research · doi:10.1038/s41413-024-00375-z · Cited by 207
Chen, M., Pratt, C. P., Zeeman, M. E., Schultz, N. D., Taylor, B. S., O’Neill, A., Castillo-Martín, M., Nowak, D. G., Naguib, A., Grace, D., et al. (2011) · Cancer Cell · doi:10.1016/j.ccr.2011.07.013 · Cited by 178
Aneuploidy as a promoter and suppressor of malignant growth
Vasudevan, A., Schukken, K. M., Sausville, E. L., Girish, V., Adebambo, O. A., & Sheltzer, J. M. (2021) · Nature reviews. Cancer · doi:10.1038/s41568-020-00321-1 · Cited by 176
Rho GTPases modulate malignant transformation of tumor cells
Orgaz, J. L., Herráiz, C., & Sanz‐Moreno, V. (2014) · Small GTPases · doi:10.4161/sgtp.29019 · Cited by 192
“Therefore, senescence has been proposed as a barrier that tumor cells need to evade in order to sustaining aberrant proliferation.(180) The characteristic morphologic changes that senescent cells undergo—flattening and enlarged cell shapes—hint toward a role of Rho GTPases in this cytoskeletal reorganization.”
BackgroundThe Transcription Factor FOXM1 (Forkhead box M1)
Wierstra, I. (2013) · Advances in cancer research · doi:10.1016/b978-0-12-407173-5.00004-2 · Cited by 180
Lee, J.-J., Kim, B. C., Park, M.-J., Lee, Y., Kim, Y.-N., Lee, B. L., & Js, L. (2010) · Cell Death and Differentiation · doi:10.1038/cdd.2010.139 · Cited by 179
“The initial description of cellular senescence by Hayflick and Moorehead was based on the endurable analysis of normal human cells grown in vitro.(8) In contrast to cancer cells, they observed that normal cells had a finite proliferative capacity that ended in stable and long-term cell cycle arrest.”
BackgroundDetection of Senescence-Associated Heterochromatin Foci (SAHF)
Aird, K. M., & Zhang, R. (2012) · Methods in molecular biology · doi:10.1007/978-1-62703-239-1_12 · Cited by 185
Knight, T., & Irving, J. A. E. (2014) · Frontiers in Oncology · doi:10.3389/fonc.2014.00160 · Cited by 164
Paracrine cellular senescence exacerbates biliary injury and impairs regeneration
Ferreira-Gonzalez, S., Lu, W.-Y., Raven, A., Dwyer, B., Man, T. Y., O’Duibhir, E., Lewis, P. J. S., Campana, L., Kendall, T. J., Bird, T. G., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-03299-5 · Cited by 161
Dynamic Modelling of Pathways to Cellular Senescence Reveals Strategies for Targeted Interventions
Pezze, P. D., Nelson, G., Otten, E. G., Korolchuk, V. I., Kirkwood, T. B. L., von Zglinicki, T., & Shanley, D. P. (2014) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1003728 · Cited by 167
Cancer research: past, present and future
Cao, Y., DePinho, R. A., Ernst, M., & Vousden, K. H. (2011) · Nature reviews. Cancer · doi:10.1038/nrc3138 · Cited by 170
Chinta, S. J., Lieu, C. A., DeMaria, M., Laberge, R. ‐., Campisi, J., & Andersen, J. K. (2013) · Journal of Internal Medicine · doi:10.1111/joim.12029 · Cited by 165
“Various forms of oxidative stress can induce senescence, including exposure to ROS and hyperoxia [26, 31, 33] (Figure 1).”
Regulation of senescence traits by MAPKs
Anerillas, C., Abdelmohsen, K., & Gorospe, M. (2020) · GeroScience · doi:10.1007/s11357-020-00183-3 · Cited by 172
“Among its benefits, senescence contributes to embryonic development, wound healing, and tumor suppression in young persons (Collado and Serrano 2010; Munoz-Espin et al. 2013; Storer et al. 2013; Demaria et al. 2014).”
Chicas, A., Kapoor, A., Wang, X., Aksoy, O., Evertts, A. G., Zhang, M. Q., Garcia, B. A., Bernstein, E., & Lowe, S. W. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1119836109 · Cited by 162
“C senescence is an antiproliferative stress-response program that acts as a potent tumor-suppressor mechanism (1).”
BackgroundFluctuations in p53 Signaling Allow Escape from Cell-Cycle Arrest
Reyes, J., Chen, J.-Y., Stewart-Ornstein, J., Karhohs, K. W., Mock, C. S., & Lahav, G. (2018) · Molecular Cell · doi:10.1016/j.molcel.2018.06.031 · Cited by 149
“The long-term maintenance of cell-cycle arrest has emerged as a critical factor for the success of cytotoxic chemotherapy (Collado and Serrano, 2010; Nardella et al., 2011).”
A step-by-step microRNA guide to cancer development and metastasis
Markopoulos, G. S., Roupakia, E., Tokamani, M., Chavdoula, E., Hatziapostolou, M., Polytarchou, C., Marcu, K. B., Papavassiliou, A. G., Sandaltzopoulos, R., & Kolettas, E. (2017) · Cellular Oncology · doi:10.1007/s13402-017-0341-9 · Cited by 164
“Despite oncogene-induced senescence (OIS), which is believed to be a cancer initiating barrier [111, 114] and other tumor suppressive mechanisms, benign cancers may still develop into overt malignancies [113, 115, 118].”
BackgroundMuñoz, D. P., Yannone, S. M., Daemen, A., Sun, Y., Vakar-Lopez, F., Kawahara, M., Freund, A. M., Rodier, F., Wu, J. D., Desprez, P.-Y., et al. (2019) · JCI Insight · doi:10.1172/jci.insight.124716 · Cited by 162
“This also raises the possibility that p16 can prevent tumor formation not only by triggering senescence arrest as an early sensor of cellular stress (65), but also by precluding the induction of immune signals that may become detrimental over time if unresolved or unwarranted.”
Faces of cellular senescence in skin aging
Ho, C. Y., & Dreesen, O. (2021) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2021.111525 · Cited by 172
“Importantly, senescence is an intrinsic tumor-suppressive mechanism that limits proliferation of preneoplastic cells with irreparable DNA damage (Collado and Serrano, 2010).”
The Warburg effect version 2.0: Metabolic reprogramming of cancer stem cells
Menéndez, J. A., Joven, J., Cufí, S., Corominas-Faja, B., Oliveras‐Ferraros, C., Cuyàs, E., Martı́n-Castillo, B., López‐Bonet, E., Alarcón, T., & Vázquez‐Martín, A. (2013) · Cell Cycle · doi:10.4161/cc.24479 · Cited by 165
Histone H3.3 and its proteolytically processed form drive a cellular senescence programme
Duarte, L. F., Young, A. R. J., Wang, Z., Wu, H., Panda, T., Kou, Y., Kapoor, A., Hasson, D., Mills, N. R., Ma’ayan, A., et al. (2014) · Nature Communications · doi:10.1038/ncomms6210 · Cited by 163
Rossiello, F., Herbig, U., Longhese, M. P., Fumagalli, M., & di Fagagna, F. D. (2014) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2014.06.009 · Cited by 163
Oxidative stress, cellular senescence and ageing
Pole, A., Dimri, M., & Dimri, G. P. (2016) · AIMS molecular science · doi:10.3934/molsci.2016.3.300 · Cited by 168
“In addition, most DNA damaging and oncogenic signals strongly provoke senescence-like phenotype as an initial response in vitro and in vivo, suggesting potential tumor suppressor role of senescence [158].”
BackgroundFrailty, aging, and periodontal disease: Basic biologic considerations
Clark, D. L., Kotronia, E., & Ramsay, S. E. (2021) · Periodontology 2000 · doi:10.1111/prd.12380 · Cited by 162
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
p53 and metabolism: from mechanism to therapeutics
Simabuco, F. M., Morale, M. G., Pavan, I. C. B., Morelli, A. P., Silva, F. R., & Tamura, R. E. (2018) · Oncotarget · doi:10.18632/oncotarget.25267 · Cited by 159
“The senescent cells can be cleared by immune cells and have a more efficient tumor regression [149].”
A set of miRNAs participates in the cellular senescence program in human diploid fibroblasts
Faraonio, R., Salerno, P., Passaro, F., Sedia, C., Iaccio, A., Bellelli, R., Nappi, T. C., Comegna, M., Romano, S., Salvatore, G., et al. (2011) · Cell Death and Differentiation · doi:10.1038/cdd.2011.143 · Cited by 150
“Since then, replicative senescence has been described in various mammalian cells.(2) The mechanisms underlying senescence include telomere shortening, upregu-”
BackgroundRare Codons Regulate KRas Oncogenesis
Lampson, B. L., Pershing, N. L., Prinz, J. A., Lacsina, J. R., Marzluff, W. F., Nicchitta, C. V., MacAlpine, D. M., & Counter, C. M. (2012) · Current Biology · doi:10.1016/j.cub.2012.11.031 · Cited by 149
“However, untransformed cells are sensitive to oncogenic stress [35], and increasing levels of transgenic HrasG12V result in progressively more growth arrested (senescent) cells and fewer mammary lesions in mice [36].”
β-Hydroxybutyrate Prevents Vascular Senescence through hnRNP A1-Mediated Upregulation of Oct4
Han, Y., Bédarida, T., Ding, Y., Somba, B. K., Lu, Q., Wang, Q., Song, P., & Zou, M. (2018) · Molecular Cell · doi:10.1016/j.molcel.2018.07.036 · Cited by 148
Oncogene- and tumor suppressor gene-mediated suppression of cellular senescence
Larsson, L. (2011) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2011.10.005 · Cited by 152
Senescent cells communicate via intercellular protein transfer
Biran, A., Perelmutter, M., Gal, H., Burton, D. G. A., Ovadya, Y., Vadai, E., Geiger, T., & Krizhanovsky, V. (2015) · Genes & Development · doi:10.1101/gad.259341.115 · Cited by 139
“In response to these stimuli, cells activate p53 and pRb pathways to permanently arrest cell proliferation and thereby block tumorigenesis (Collado and Serrano 2010; Freund et al. 2010; Kuilman et al. 2010; Salama et al. 2014).”
Hepatocellular carcinoma in nonalcoholic fatty liver: role of environmental and genetic factors
Dongiovanni, P. (2014) · World Journal of Gastroenterology · doi:10.3748/wjg.v20.i36.12945 · Cited by 145
The Role of Antioxidants in the Interplay between Oxidative Stress and Senescence
Varesi, A., Chirumbolo, S., Campagnoli, L. I. M., Pierella, E., Piccini, G. B., Carrara, A., Ricevuti, G., Scassellati, C., Bonvicini, C., & Pascale, A. (2022) · Antioxidants · doi:10.3390/antiox11071224 · Cited by 145
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 147
“Overall, p53 is found to favor immunosurveillance in different settings both directly and indirectly (Collado & Serrano, 2010; Gorgoulis & Halazonetis, 2010; Salama et al., 2014).”
BackgroundDerepression of hTERT gene expression promotes escape from oncogene-induced cellular senescence
Patel, P. L., Suram, A., Mirani, N., Bischof, O., & Herbig, U. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1602379113 · Cited by 142
“We and others have demonstrated that the reasons for the inactive nature of certain human cancer precursor lesions is because cells within these lesions had undergone cellular senescence (1, 2).”
BackgroundClinical landscape of cancer metastases
Riihimäki, M., Thomsen, H., Sundquist, K., Sundquist, J., & Hemminki, K. (2018) · Cancer Medicine · doi:10.1002/cam4.1697 · Cited by 144
Poblocka, M., Bassey, A. L., Smith, V. M., Falcicchio, M., Manso, A. S., Althubiti, M., Sheng, X., Kyle, A., Barber, R., Frigerio, M., et al. (2021) · Scientific Reports · doi:10.1038/s41598-021-99852-2 · Cited by 137
The role of adipose tissue senescence in obesity- and ageing-related metabolic disorders
Liu, Z., Wu, K. K.-L., Jiang, X. X., Xu, A., & Cheng, K. K. Y. (2020) · Clinical Science · doi:10.1042/cs20190966 · Cited by 148
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 146
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 138
“Consistent with this notion, senescent cells are found in pre-malignant tissues, both in mouse models and human benign tumors, yet almost absent in malignant ones [75].”
BackgroundLee, J., & Lee, J. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23094843 · Cited by 151
Cellular senescence and cancer chemotherapy resistance
Gordon, R. R., & Nelson, P. S. (2012) · Drug Resistance Updates · doi:10.1016/j.drup.2012.01.002 · Cited by 138
“In addition to the visible physical changes there is an increased activity of senescence associated β-galactosidase present within the cells (Collado and Serrano, 2010).”
BackgroundBiomarkers and Molecular Probes for Cell Death Imaging and Targeted Therapeutics
Smith, B. D., & Smith, B. D. (2012) · Bioconjugate Chemistry · doi:10.1021/bc3003309 · Cited by 135
Pinho, A. V., Rooman, I., Reichert, M., De Medts, N., Bouwens, L., Rustgi, A. K., & Real, F. X. (2011) · Gut · doi:10.1136/gut.2010.225920 · Cited by 129
“Apoptosis, demonstrated by the detection of activated caspase 3, was found to be only a minor contributor, leading us to consider the activation of a senescence programme.(15) Indeed, we found an upregulation of classical senescence markers during in vitro culture, in marked contrast with their absence in normal pancr…”
BackgroundInfluentialWilms tumor 1 (WT1) regulates KRAS-driven oncogenesis and senescence in mouse and human models
Vicent, S., Ron, C., Sayles, L. C., Lin, C., Walker, R. G., Gillespie, A. K., Subramanian, A., Hinkle, G., Yang, X., Saif, S., et al. (2010) · Journal of Clinical Investigation · doi:10.1172/jci44165 · Cited by 131
“Activation of the RAS pathway can lead to either proliferation or senescence (6, 7).”
BackgroundRole of Cellular Senescence in Type II Diabetes
Narasimhan, A., Flores, R. R., Robbins, P. D., & Niedernhofer, L. J. (2021) · Endocrinology · doi:10.1210/endocr/bqab136 · Cited by 133
Deoxysphingolipids, Novel Biomarkers for Type 2 Diabetes, Are Cytotoxic for Insulin-Producing Cells
Zuellig, R. A., Hornemann, T., Othman, A., Hehl, A. B., Bode, H., Güntert, T., Ogunshola, O. O., Saponara, E., Grabliauskaite, K., Jang, J., et al. (2013) · Diabetes · doi:10.2337/db13-1042 · Cited by 131
Ni, T., Li, X.-Y., Lu, N., An, T., Liu, Z., Fu, R., Lv, W.-C., Zhang, Y.-W., Xu, X.-J., Rowe, R. G., et al. (2016) · Nature Cell Biology · doi:10.1038/ncb3425 · Cited by 129
Calcium signaling and cellular senescence
Martin, N., & Bernard, D. (2017) · Cell Calcium · doi:10.1016/j.ceca.2017.04.001 · Cited by 133
Evangelou, K., & Gorgoulis, V. G. (2017) · Methods in Molecular Biology · doi:10.1007/978-1-4939-6670-7_10 · Cited by 124
Biology of Cancer and Aging: A Complex Association With Cellular Senescence
Falandry, C., Bonnefoy, M., Freyer, G., & Gilson, É. (2014) · Journal of Clinical Oncology · doi:10.1200/jco.2014.55.1432 · Cited by 133
Glycolysis, the sweet appetite of the tumor microenvironment
Kooshan, Z., Cárdenas-Piedra, L., Clements, J. A., & Batra, J. (2024) · Cancer Letters · doi:10.1016/j.canlet.2024.217156 · Cited by 135
Cindrova-Davies, T., Fogarty, N. M. E., Jones, C. J. P., Kingdom, J., & Burton, G. J. (2018) · Placenta · doi:10.1016/j.placenta.2018.06.307 · Cited by 127
Kumar, M., Seeger, W., & Voswinckel, R. (2014) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2013-0382ps · Cited by 131
“Collado and Serrano have provided evidence confirming the tumor suppressor nature of senescence response in mice and humans (52).”
BackgroundFOXM1 targets NBS1 to regulate DNA damage-induced senescence and epirubicin resistance
Khongkow, P., Karunarathna, U., Khongkow, M., Gong, C., Gomes, A., Yagüe, E., Monteiro, L. J., Kongsema, M., Zona, S., Man, E. P. S., et al. (2013) · Oncogene · doi:10.1038/onc.2013.457 · Cited by 131
“overcome cellular senescence and achieved immortality (12).”
BackgroundSingle-cell transcriptomics identifies Mcl-1 as a target for senolytic therapy in cancer
Troiani, M., Colucci, M., D’Ambrosio, M., Guccini, I., Pasquini, E., Varesi, A., Valdata, A., Mosole, S., Revandkar, A., Attanasio, G., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-29824-1 · Cited by 134
“…tumor cells at single-cells resolution, we de fi ned a senescence signature by combining the expression of p16 INK4a , p15 INK4b , p19 Arf , p21 Waf1/Cip1 , p27 Kip1 , and PAI-1 , the most upregulated senescent markers in whole tumors lysates, as detected by western blot analysis 1,21 (Fig.”
Cell senescence contributes to tissue regeneration in zebrafish
Da Silva‐Álvarez, S., Guerra‐Varela, J., Sobrido‐Cameán, D., Quelle, A., Barreiro‐Iglesias, A., Sánchez, L., & Collado, M. (2020) · Aging Cell · doi:10.1111/acel.13052 · Cited by 126
“This is consid‐ ered the basis of its tumor‐suppressive function (Collado et al., 2007; Collado & Serrano, 2010).”
BackgroundSelf-citationAge- and tissue-specific expression of senescence biomarkers in mice.
Hudgins, A. D., Tazearslan, C., Tare, A., Zhu, Y., Huffman, D., & Suh, Y. (2018) · Frontiers in Genetics · doi:10.3389/fgene.2018.00059 · Cited by 124
“, 2008), and tumor suppression (Collado and Serrano, 2010), as well as age-related disorders (Childs et al.”
BackgroundSmall-molecule MDM2 antagonists attenuate the senescence-associated secretory phenotype
Wiley, C. D., Schaum, N., Alimirah, F., Lopez-Dominguez, J. A., Orjalo, A. V., Scott, G., Desprez, P.-Y., Benz, C., Davalos, A. R., & Campisi, J. (2018) · Scientific Reports · doi:10.1038/s41598-018-20000-4 · Cited by 124
Heilmann, A. M., Perera, R. M., Ecker, V., Nicolay, B. N., Bardeesy, N., Benes, C. H., & Dyson, N. J. (2014) · Cancer Research · doi:10.1158/0008-5472.can-13-2923 · Cited by 119
Senescent Carcinoma-Associated Fibroblasts Upregulate IL8 to Enhance Prometastatic Phenotypes
Wang, T., Notta, F., Navab, R., Joseph, J., Ibrahimov, E., Xu, J., Zhu, C.-Q., Borgida, A., Gallinger, S., & Tsao, M.-S. (2017) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-16-0192 · Cited by 123
“Cell lines, tissue, and mouse strains This study was approved by the Research Ethics Board of the UniversityHealthNetwork (13-6377).”
MethodWang, Z., Ma, L., Su, M., Zhou, Y., Mao, K., Li, C., Peng, G., Zhou, C., Shen, B., & Dou, J. (2018) · Cell Death and Disease · doi:10.1038/s41419-017-0223-0 · Cited by 122
Fard, M. T., & Stough, C. K. K. (2019) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2019.00056 · Cited by 124
Cellular senescence in lung cancer: Molecular mechanisms and therapeutic interventions
Jha, S. K., Rubis, G. D., Devkota, S. R., Zhang, Y., Adhikari, R., Jha, L. A., Bhattacharya, K., Mehndiratta, S., Gupta, G., Singh, S. K., et al. (2024) · Ageing Research Reviews · doi:10.1016/j.arr.2024.102315 · Cited by 138
“Senescence is best recognized for boxing a robust anticancer mechanism that inhibits the growth of pre-neoplastic cells, hence preventing cancers (Collado and Serrano, 2010).”
Stressing the cell cycle in senescence and aging
Chandler, H., & Peters, G. (2013) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2013.07.005 · Cited by 119
Human RECQ helicases: Roles in DNA metabolism, mutagenesis and cancer biology
Monnat, R. J. (2010) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2010.10.002 · Cited by 127
Mechanisms of Immune Signaling in Colitis-Associated Cancer
Waldner, M. J., & Neurath, M. F. (2014) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2014.11.006 · Cited by 119
“Mutations affecting TP53 occur at late stages of sporadic CRC, usually resulting in loss of p53 function, bypass of senescence, and infiltrative and metastatic tumor growth.(37,38) In contrast to sporadic CRC, TP53 mutations occur at early steps of CAC,”
BackgroundRoles and mechanisms of cellular senescence in regulation of tissue homeostasis
Ohtani, N., & Hara, E. (2013) · Cancer Science · doi:10.1111/cas.12118 · Cited by 122
Paramos-de-Carvalho, D., Jacinto, A., & Saúde, L. (2021) · eLife · doi:10.7554/elife.72449 · Cited by 111
“Cancer Cellular senescence is a powerful barrier to tumourigenesis (Collado and Serrano, 2010).”
BackgroundCellular senescence predicts treatment outcome in metastasised colorectal cancer
Haugstetter, A. M., Loddenkemper, C., Lenze, D., Gröne, J., Standfuß, C., Petersen, I., Dörken, B., & Schmitt, C. A. (2010) · British Journal of Cancer · doi:10.1038/sj.bjc.6605784 · Cited by 117
“…growth condition is oncogene-induced senescence (OIS), a terminal cell-cycle arrest initiated by activated Ras-type oncogenes that functions as a tumour-suppressive barrier in pre-malignant lesions in vivo (Braig et al, 2005; Michaloglou et al, 2005; Collado and Serrano, 2010; Reimann et al, 2010).”
BackgroundRan GTPase: A Key Player in Tumor Progression and Metastasis
Boudhraa, Z., Carmona, E., Provencher, D. M., & Mes‐Masson, A. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.00345 · Cited by 117
“Briefly, senescence is a state during which cells enter into an irreversible non-proliferative but viable state (Collado and Serrano, 2010; Hanahan and Weinberg, 2011).”
BackgroundThe Rho GTPase Rnd1 suppresses mammary tumorigenesis and EMT by restraining Ras-MAPK signalling
Okada, T., Sinha, S., Esposito, I., Schiavon, G., López-Lago, M. A., Su, W., Pratilas, C. A., Abele, C., Hernandez, J. M., Ohara, M., et al. (2014) · Nature Cell Biology · doi:10.1038/ncb3082 · Cited by 117
Preclinical antitumor efficacy of senescence-inducing chemotherapy combined with a nanoSenolytic
Galiana, I., Lozano‐Torres, B., Sancho, M., Alfonso, M., Bernardos, A., Bisbal, V., Serrano, M., Martínez‐Máñez, R., & Orzáez, M. (2020) · Journal of Controlled Release · doi:10.1016/j.jconrel.2020.04.045 · Cited by 119
Self-citationThe 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 125
“The most common view is that OIS is an early protective barrier to prevent excessive proliferation of transformed cells, before telomeric abnormalities take effect (Collado and Serrano, 2010; Peeper, 2011).”
BackgroundBai, X., Fisher, D. E., & Flaherty, K. T. (2019) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-019-0204-6 · Cited by 107
Yan, Z., Ohuchida, K., Fei, S., Zheng, B., Guan, W., Feng, H., Kibe, S., Ando, Y., Koikawa, K., Abe, T., et al. (2019) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-019-1226-8 · Cited by 113
“The protein p16 is a major player in cellular response to DNA damage, which leads to senescence [48] and/or apoptosis [49, 50].”
BackgroundLiu, X., Hoft, D. F., & Peng, G. (2020) · Journal of Clinical Investigation · doi:10.1172/jci133679 · Cited by 116
Senescent Cells and Their Secretory Phenotype as Targets for Cancer Therapy
Velarde, M. C., Demaria, M., & Campisi, J. (2013) · Interdisciplinary Topics in Gerontology and Geriatrics · doi:10.1159/000343572 · Cited by 112
“The induction and maintenance of the senescence growth arrest depend on the functions of both the Arf/p53/p21 and p16/pRb tumor suppressor pathways [26].”
BackgroundCellular Senescence - its role in cancer and the response to ionizing radiation
Sabin, R. J., & Anderson, R. M. (2011) · Genome Integrity · doi:10.1186/2041-9414-2-7 · Cited by 123
“both mice and human studies [13].”
Efimova, E. V., Mauceri, H. J., Golden, D. W., Labay, E., Bindokas, V. P., Darga, T. E., Chakraborty, C., Barreto-Andrade, J. C., Crawley, C. D., Sutton, H. G., et al. (2010) · Cancer Research · doi:10.1158/0008-5472.can-09-4224 · Cited by 118
“Whereas it remains a dogma that IR and genotoxic agents mediate their lethal effects via enhanced apoptosis, necrosis, or mitotic catastrophe, senescence is an alternative terminal phenotype that may be highly relevant as a determinant of outcomes for cancer treatment (16, 22, 23).”
Kinase-Impaired BRAF Mutations in Lung Cancer Confer Sensitivity to Dasatinib
Sen, B., Peng, S., Tang, X., Erickson, H. S., Galindo, H., Mazumdar, T., Stewart, D. J., Wistuba, I. I., & Johnson, F. M. (2012) · Science Translational Medicine · doi:10.1126/scitranslmed.3003513 · Cited by 110
Detecting and targeting senescent cells using molecularly imprinted nanoparticles
Ekpenyong‐Akiba, A. E., Canfarotta, F., Bashar Abd, H., Poblocka, M., Casulleras, M., Castilla‐Vallmanya, L., Kocsis‐Fodor, G., Kelly, M. E., Janus, J., Althubiti, M., et al. (2019) · Nanoscale Horizons · doi:10.1039/c8nh00473k · Cited by 111
Epithelial-mesenchymal transition and senescence: two cancer-related processes are crossing paths
Smit, M. A., & Peeper, D. S. (2010) · Aging · doi:10.18632/aging.100209 · Cited by 106
Cooperation between p21 and Akt is required for p53‐dependent cellular senescence
Kim, Y. Y., Jee, H. J., Um, J., Kim, Y. M., Bae, S. S., & Yun, J. (2017) · Aging Cell · doi:10.1111/acel.12639 · Cited by 105
“…is known to contribute to organismal aging processes, another type of cellular senescence, termed ‘premature senescence’ or ‘stress-induced senescence’, is considered a barrier to tumorigenesis because it acts to remove precancerous cells (Collado et al., 2005; Collado & Serrano, 2010).”
BackgroundYang, S., Hwang, S., Kim, M., Seo, S. B., Lee, J., & Jeong, S. M. (2018) · Cell Death and Disease · doi:10.1038/s41419-017-0089-1 · Cited by 108
Ras signaling through RASSF proteins
Donninger, H., Schmidt, M., Mezzanotte-Sharpe, J., Barnoud, T., & Clark, G. J. (2016) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2016.06.007 · Cited by 110
The Yin and Yang functions of the Myc oncoprotein in cancer development and as targets for therapy
Larsson, L., & Arsenian‐Henriksson, M. (2010) · Experimental Cell Research · doi:10.1016/j.yexcr.2010.03.025 · Cited by 106
Hiraoka, K., Inoue, T., Taylor, R. D., Watanabe, T., Koshikawa, N., Yoda, H., Shinohara, K., Takatori, A., Sugimoto, H., Maru, Y., et al. (2015) · Nature Communications · doi:10.1038/ncomms7706 · Cited by 103
Chromatin basis of the senescence-associated secretory phenotype
Hao, X., Wang, C., & Zhang, R. (2022) · Trends in Cell Biology · doi:10.1016/j.tcb.2021.12.003 · Cited by 94
Tato-Costa, J., Casimiro, S., Pacheco, T. R., Pires, R., Fernandes, A., Alho, I., Pereira, P., Costa, P., Castelo, H. B., Ferreira, J. A., et al. (2015) · Clinical Colorectal Cancer · doi:10.1016/j.clcc.2015.09.003 · Cited by 107
“Also, the treatment of patients with cancer using DNA-damaging agents, in both neoadjuvant and curative settings, was shown to induce epithelial cancer cells into accelerated forms of senescence.(14)”
BackgroundLoss of MT1-MMP causes cell senescence and nuclear defects which can be reversed by retinoic acid
Gutiérrez‐Fernández, A., Soria‐Valles, C., Osorio, F. G., Gutiérrez‐Abril, J., Garabaya, C., Aguirre, A., Fueyo, A., Fernández‐García, M. S., Puente, X. S., & López‐Otín, C. (2015) · The EMBO Journal · doi:10.15252/embj.201490594 · Cited by 96
“The tumor suppressor protein p16 INK4a , a marker of cellular senescence (Collado & Serrano, 2010; Krishnamurthy et al , 2004), showed a strong accumulation in fibroblasts derived from Mmp14 (cid:1) / (cid:1) mice (Fig 1F).”
Tran, P. T., Shroff, E. H., Burns, T. F., Thiyagarajan, S., Das, S., Zabuawala, T., Chen, J., Cho, Y., Luong, R. H., Tamayo, P., et al. (2012) · PLoS Genetics · doi:10.1371/journal.pgen.1002650 · Cited by 108
“One such pathway is oncogene-induced senescence (OIS), a failsafe program that prevents normal cells from progressing towards malignancy following introduction of a mutant form of an oncogene such as Kras [17].”
Venturelli, S., Berger, A., Weiland, T., Eßmann, F., Waibel, M., Nuebling, T., Häcker, S., Schenk, M., Schulze‐Osthoff, K., Salih, H. R., et al. (2013) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-13-0137 · Cited by 103
“Noteworthy, in comparison with the in vitro situation senescent cells often lack to display all classical markers of senescence in vivo (9).”
BackgroundConstitutive HER2 Signaling Promotes Breast Cancer Metastasis through Cellular Senescence
Angelini, P. D., Fluck, M. F. Z., Pedersen, K., Parra-Palau, J. L., Guiu, M., Morales, C. B., Vicario, R., Luque-García, A., Navalpotro, N. P., Giralt, J., et al. (2013) · Cancer Research · doi:10.1158/0008-5472.can-12-2301 · Cited by 104
“org Cancer Res; 73(1) January 1, 2013 455”
BackgroundInfluentialCooperation and Antagonism among Cancer Genes: The Renal Cancer Paradigm
Peña‐Llopis, S., Christie, A. L., Xie, X.-J., & Brugarolas, J. (2013) · Cancer Research · doi:10.1158/0008-5472.can-13-0360 · Cited by 101
“induce senescence or proliferation (34).”
Transcriptional regulation of cellular senescence
Lanigan, F., Geraghty, J. G., & Bracken, A. P. (2011) · Oncogene · doi:10.1038/onc.2011.34 · Cited by 95
“This phenomenon, known as ‘replicative senescence’ because it correlates with telomere attrition (Harley et al., 1990), has since been observed in multiple cell types from several different organisms (Collado and Serrano, 2010).”
Vázquez‐Martín, A., Vellón, L., Quirós, P. M., Cufí, S., de Galarreta, E. R., Oliveras‐Ferraros, C., Martín, Á. G., Martı́n-Castillo, B., López-Otı́n, C., & Menéndez, J. A. (2012) · Cell Cycle · doi:10.4161/cc.11.5.19450 · Cited by 98
“Reprogramming-induced senescence (RIS) is a crucial reprogramming barrier in response to the expression of stem-cellspecific genes that mimics the senescence response observed during oncogene-induced senescence (OIS) in primary cells, which limits oncogenic transformation.(2,23-27) When senescence is disabled, the cel…”
Background
Metadata
- 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
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › 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
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
