WNT16B Is a New Marker of Cellular Senescence That Regulates p53 Activity and the Phosphoinositide 3-Kinase/AKT Pathway
Open accessPublished version of a preprint
Abstract
Senescence is a tumor suppression mechanism that is induced by several stimuli, including oncogenic signaling and telomere shortening, and controlled by the p53/p21WAF1 signaling pathway. Recently, a critical role for secreted factors has emerged, suggesting that extracellular signals are necessary for the onset and maintenance of senescence. Conversely, factors secreted by senescent cells may promote tumor growth. By using expression profiling techniques, we searched for secreted factors that were overexpressed in fibroblasts undergoing replicative senescence. We identified WNT16B, a member of the WNT family of secreted proteins. We found that WNT16B is overexpressed in cells undergoing stress-induced premature senescence and oncogene-induced senescence in both MRC5 cell line and the in vivo murine model of K-RasV12–induced senescence. By small interfering RNA experiments, we observed that both p53 and WNT16B are necessary for the onset of replicative senescence. WNT16B expression is required for the full transcriptional activation of p21WAF1. Moreover, WNT16B regulates activation of the phosphoinositide 3-kinase (PI3K)/AKT pathway. Overall, we identified WNT16B as a new marker of senescence that regulates p53 activity and the PI3K/AKT pathway and is necessary for the onset of replicative senescence. [Cancer Res 2009;69(24):9183–91]
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Secreted WNT16B is an important enforcer of the senescence growth arrest of human fibroblasts in culture and of mouse cells that senesce in vivo due to activated RAS.
“Likewise, secreted WNT16B is an important enforcer of the senescence growth arrest of human fibroblasts in culture, as well as that of mouse cells that senesce in vivo owing to expression of an activated RAS oncogene (138).”
From Aging, Cellular Senescence, and Cancer (2013) · cites this paper as [138]
The Results section, “WNT16B is necessary for the onset of replicative senescence” (page unavailable), reports that WNT16B knockdown let cultured human fibroblasts bypass senescence and continue proliferating. The Results section, “WNT16 is activated in OIS in vitro and in vivo” (page unavailable), finds WNT16B overexpressed in activated-K-Ras mouse lung lesions, but identifies it there as a marker; it does not show that WNT16B enforces growth arrest in those mouse cells. (LLM, conf=0.90)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
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
The limited in vitro lifetime of human diploid cell strains
Hayflick, L. (1965) · Experimental Cell Research · doi:10.1016/0014-4827(65)90211-9 · Cited by 5,876 · see citing works
The Wnt Signaling Pathway in Development and Disease
Logan, C. Y., & Nusse, R. (2004) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.20.010403.113126 · Cited by 5,325 · see citing works
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 5,178 · cited 4× · see citing works
“HRas (8, 23), or irradiated with X-rays (25 Gy).”
BackgroundInfluentialSelf-citationExtension of Life-Span by Introduction of Telomerase into Normal Human Cells
Bodnar, A. G., Ouellette, M., Frolkis, M., Holt, S. E., Chiu, C.-P., Morin, G. B., Harley, C. B., Shay, J. W., Lichtsteiner, S., & Wright, W. E. (1998) · Science · doi:10.1126/science.279.5349.349 · Cited by 4,975 · see citing works
A System for Stable Expression of Short Interfering RNAs in Mammalian Cells
Brummelkamp, T. R., Bernards, R., & Agami, R. (2002) · Science · doi:10.1126/science.1068999 · Cited by 4,295 · 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
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
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 1× · see citing works
“org Downloaded from cence (SIPS), can be induced by events such as DNA damage (4), oxidative stress (5), epigenetic modifications (6), or cytokine stimulation (7).”
BackgroundSenescence in premalignant tumours
Collado, M., Gil, J., Efeyan, A., Guerra, C., Schuhmacher, A. J., Barradas, M., Benguría, A., Zaballos, A., Flores, J. M., Barbacid, M., et al. (2005) · Nature · doi:10.1038/436642a · Cited by 1,482 · see citing works
Self-citationHerbig, U., Jobling, W. A., Chen, B. P. C., Chen, D. J., & Sedivy, J. M. (2004) · Molecular Cell · doi:10.1016/s1097-2765(04)00256-4 · Cited by 1,344 · cited 1× · see citing works
“org Downloaded from the activation of the p53 transcription factor (34).”
BackgroundDi Leonardo, A., Linke, S. P., Clarkin, K., & Wahl, G. M. (1994) · Genes & Development · doi:10.1101/gad.8.21.2540 · Cited by 1,215 · see citing works
Living on a break: cellular senescence as a DNA-damage response
d'Adda di Fagagna, F. (2008) · Nature Reviews Cancer · doi:10.1038/nrc2440 · Cited by 1,170 · see citing works
Wnt signaling in disease and in development
Nusse, R. (2005) · Cell Research · doi:10.1038/sj.cr.7290260 · Cited by 974 · see citing works
Wajapeyee, N., Serra, R. W., Zhu, X., Mahalingam, M., & Green, M. R. (2008) · Cell · doi:10.1016/j.cell.2007.12.032 · Cited by 903 · see citing works
Nogueira, V., Park, Y., Chen, C.-C., Xu, P.-Z., Chen, M.-L., Tonic, I., Unterman, T., & Hay, N. (2008) · Cancer Cell · doi:10.1016/j.ccr.2008.11.003 · Cited by 780 · see citing works
Augmented Wnt signaling in a mammalian model of accelerated aging
Liu, H., Fergusson, M. M., Castilho, R. M., Liu, J., Cao, L., Chen, J., Malide, D., Rovira, I. I., Schimel, D., Kuo, C. J., et al. (2007) · Science · doi:10.1126/science.1143578 · Cited by 755 · see citing works
Senescence-like growth arrest induced by hydrogen peroxide in human diploid fibroblast F65 cells.
Chen, Q., & Ames, B. N. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.10.4130 · Cited by 641 · see citing works
Kortlever, R. M., Higgins, P. J., & Bernards, R. (2006) · Nature Cell Biology · doi:10.1038/ncb1448 · Cited by 637 · cited 2× · see citing works
“Plasminogen activator inhibitor-1 (PAI-1) is required to induce replicative senescence in fibroblasts in an autocrine fashion (10).”
BackgroundTumor induction by an endogenous K-ras oncogene is highly dependent on cellular context
Guerra, C. E., Mijimolle, N., Dhawahir, A., Dubus, P. R., Barradas, M., Serrano, M., Campuzano, V., & Barbacid, M. (2003) · Cancer Cell · doi:10.1016/s1535-6108(03)00191-0 · Cited by 566 · see citing works
Self-citationMethods to Detect Biomarkers of Cellular Senescence
Itahana, K., Campisi, J., & Dimri, G. P. (2007) · Methods in molecular biology · doi:10.1007/978-1-59745-361-5_3 · Cited by 516 · see citing works
(1995) · PubMed · Cited by 496 · see citing works
Telomere dysfunction and tumour suppression: the senescence connection
Deng, Y., Chan, S. S., & Chang, S. (2008) · Nature Reviews Cancer · doi:10.1038/nrc2393 · Cited by 411 · see citing works
Dissanayake, S. K., Wade, M. S., Johnson, C. E., O’Connell, M. P., Leotlela, P. D., French, A. D., Shah, K. V., Hewitt, K. J., Rosenthal, D. T., Indig, F. E., et al. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m700075200 · Cited by 374 · see citing works
Mechanisms of cellular senescence in human and mouse cells.
Itahana, K., Campisi, J., & Dimri, G. P. (2004) · Biogerontology · doi:10.1023/b:bgen.0000017682.96395.10 · Cited by 338 · cited 1× · see citing works
“Depending on the type of inducer, cellular senescence is initiated through two complementary tumor suppressor pathways, p53 or p16, both pathways leading to irreversible cell cycle arrest (9).”
BackgroundCoppé, 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 · see citing works
Halbert, C. L., Demers, G. W., & Galloway, D. A. (1992) · Journal of Virology · doi:10.1128/jvi.66.4.2125-2134.1992 · Cited by 277 · see citing works
Ye, X., Zerlanko, B. J., Kennedy, A. L., Gowrishankar, B., Zhang, R., & Adams, P. D. (2007) · Molecular Cell · doi:10.1016/j.molcel.2007.05.034 · Cited by 227 · see citing works
Kim, K. S., Seu, Y. B., Baek, S.-H., Kim, M. J., Kim, K. J., Kim, J. H., & Kim, J.-R. (2007) · Molecular Biology of the Cell · doi:10.1091/mbc.e07-03-0280 · Cited by 199 · see citing works
Ying, J., Li, H., Yu, J. Q., Ng, K. M., Poon, F. F., Wong, S. C. C., Chan, A. T. �., Sung, J. J. �., & Tao, Q. (2008) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-07-1644 · Cited by 193 · see citing works
The Wnt signaling pathway: Aging gracefully as a protectionist?
Maiese, K., Li, F., Chong, Z. Z., & Shang, Y. (2008) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2008.01.004 · Cited by 170 · see citing works
Jiang, H., Schiffer, E., Song, Z., Wang, J., Zürbig, P., Thedieck, K., Moes, S., Bantel, H., Saal, N., Jantos, J., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0801457105 · Cited by 169 · see citing works
ING2 Regulates the Onset of Replicative Senescence by Induction of p300-Dependent p53 Acetylation
Pedeux, R., Sengupta, S., Shen, J., Demidov, O. N., Saito, S., Onogi, H., Kumamoto, K., Wincovitch, S., Garfield, S. H., McMenamin, M., et al. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.15.6639-6648.2005 · Cited by 121 · see citing works
Self-citationMazières, J., You, L., He, B., Xu, Z., Lee, A. Y., Mikami, I., McCormick, F. P., & Jablons, D. M. (2005) · Oncogene · doi:10.1038/sj.onc.1208568 · Cited by 104 · see citing works
Smurf2 up-regulation activates telomere-dependent senescence
Zhang, H., & Cohen, S. N. (2004) · Genes & Development · doi:10.1101/gad.1253004 · Cited by 100 · see citing works
MacKenzie, K. L., Franco, S., May, C., Sadelain, M., & Moore, M. A. S. (2000) · Experimental Cell Research · doi:10.1006/excr.2000.4982 · Cited by 92 · see citing works
Role for WNT16B in human epidermal keratinocyte proliferation and differentiation
Teh, M., Blaydon, D. C., Ghali, L. R., Edmunds, S., Pantazi, E., Barnes, M. R., Leigh, I. M., Kelsell, D. P., & Philpott, M. P. (2007) · Journal of Cell Science · doi:10.1242/jcs.03329 · Cited by 76 · see citing works
Wnt-16a, a Novel Wnt-16 Isoform, Which Shows Differential Expression in Adult Human Tissues
Fear, M. W., Kelsell, D. P., Spurr, N. K., & Barnes, M. R. (2000) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2000.3852 · Cited by 62 · see citing works
ING2 controls the progression of DNA replication forks to maintain genome stability
Larrieu, D., Ythier, D., Binet, R., Brambilla, C., Brambilla, E. M., Sengupta, S., & Pedeux, R. (2009) · EMBO Reports · doi:10.1038/embor.2009.180 · Cited by 42 · see citing works
Self-citationYoshikawa, H., Matsubara, K., Zhou, X., Okamura, S., Kubo, T., Murase, Y., Shikauchi, Y., Esteller, M., Herman, J. G., Wang, X. W., et al. (2007) · Molecular Biology of the Cell · doi:10.1091/mbc.e06-10-0889 · Cited by 37 · see citing works
Self-citationWnt5a and PKC, a deadly partnership involved in melanoma invasion
Medrano, E. E. (2007) · Pigment Cell Research · doi:10.1111/j.1600-0749.2007.00383.x · Cited by 10 · see citing works
Flagged first, then by citations
1 of the 43 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Aging, Cellular Senescence, and Cancer
Campisi, J. (2013) · Annual Review of Physiology · doi:10.1146/annurev-physiol-030212-183653 · Cited by 2,954 · see citing works
The role of senescent cells in ageing
van Deursen, J. M. (2014) · Nature · doi:10.1038/nature13193 · Cited by 2,623 · see citing works
Laberge, R.-M., Sun, Y., Orjalo, A. V., Patil, C. K., Freund, A., Zhou, L., Curran, S. C., Davalos, A. R., Wilson-Edell, K. A., Liu, S., et al. (2015) · Nature Cell Biology · doi:10.1038/ncb3195 · Cited by 1,160 · see citing works
Sun, Y., Campisi, J., Higano, C., Beer, T. M., Porter, P., Coleman, I., True, L., & Nelson, P. S. (2012) · Nature Medicine · doi:10.1038/nm.2890 · Cited by 793 · see citing works
Renal Aging: Causes and Consequences
O’Sullivan, E. D., Hughes, J., & Ferenbach, D. A. (2017) · Journal of the American Society of Nephrology · doi:10.1681/asn.2015121308 · Cited by 484 · see citing works
Cellular Senescence in the Kidney
Docherty, M.-H., O’Sullivan, E. D., Bonventre, J. V., & Ferenbach, D. A. (2019) · Journal of the American Society of Nephrology · doi:10.1681/asn.2018121251 · Cited by 291 · see citing works
Wnt Signalling in Implantation, Decidualisation and Placental Differentiation – Review
Sonderegger, S., Pollheimer, J., & Knöfler, M. (2010) · Placenta · doi:10.1016/j.placenta.2010.07.011 · Cited by 265 · see citing works
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
Good Manufacturing Practices Production of Mesenchymal Stem/Stromal Cells
Sensebé, L., Bourin, P., & Tarte, K. (2010) · Human Gene Therapy · doi:10.1089/hum.2010.197 · Cited by 232 · see citing works
Immune System Dysfunction in the Elderly
Eduardo Fuentes, Q., FUENTES, M., Alarcón, M. A., & Palomo, I. F. (2017) · Anais da Academia Brasileira de Ciências · doi:10.1590/0001-3765201720160487 · Cited by 234 · see citing works
Zhang, D., Wang, H., & Tan, Y. (2011) · PLoS ONE · doi:10.1371/journal.pone.0021397 · Cited by 199 · see citing works
Regulation of Survival Networks in Senescent Cells: From Mechanisms to Interventions
Soto-Gamez, A., Quax, W. J., & Demaria, M. (2019) · Journal of Molecular Biology · doi:10.1016/j.jmb.2019.05.036 · Cited by 175 · see citing works
Glucocorticoids, genes and brain function
Juszczak, G. R., & Stankiewicz, A. M. (2017) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2017.11.020 · Cited by 135 · see citing works
Evangelou, K., & Gorgoulis, V. G. (2017) · Methods in Molecular Biology · doi:10.1007/978-1-4939-6670-7_10 · Cited by 124 · see citing works
Nanoparticle modulation of the tumor microenvironment enhances therapeutic efficacy of cisplatin
Miao, L., Wang, Y., Lin, C. M., Xiong, Y., Chen, N., Zhang, L., Kim, W. Y., & Huang, L. (2015) · Journal of Controlled Release · doi:10.1016/j.jconrel.2015.08.027 · Cited by 119 · see citing works
Transient delivery of modified mRNA encoding TERT rapidly extends telomeres in human cells
Ramunas, J., Yakubov, E., Brady Jennifer, J., Corbel, S. Y., Holbrook, C., Brandt, M., Stein, J., Santiago, J. G., Cooke, J. P., & Blau, H. M. (2015) · The FASEB Journal · doi:10.1096/fj.14-259531 · Cited by 123 · see citing works
Sun, Y., Zhu, D., Chen, F., Qian, M., Wei, H., Chen, W., & Xu, J. (2016) · Oncogene · doi:10.1038/onc.2015.494 · Cited by 112 · see citing works
RetractedLabel-retaining liver cancer cells are relatively resistant to sorafenib
Xin, H.-W., Ambe, C. M., Hari, D. M., Wiegand, G. W., Miller, T. C., Chen, J., Anderson, A. J., Ray, S., Mullinax, J. E., Koizumi, T., et al. (2013) · Gut · doi:10.1136/gutjnl-2012-303261 · Cited by 109 · see citing works
Intersection of AHR and Wnt Signaling in Development, Health, and Disease
Schneider, A. J., Branam, A. M., & Peterson, R. E. (2014) · International Journal of Molecular Sciences · doi:10.3390/ijms151017852 · Cited by 106 · see citing works
Conserved senescence associated genes and pathways in primary human fibroblasts detected by RNA-seq
Marthandan, S., Baumgart, M., Priebe, S., Groth, M., Schaer, J., Kaether, C., Guthke, R., Cellerino, A., Platzer, M., Diekmann, S., et al. (2016) · PLOS ONE · doi:10.1371/journal.pone.0154531 · Cited by 91 · see citing works
“We found a high degree of similarity between common DEG among MRC-5 fibroblasts in our study and that conducted by [68], HFF strains conducted by [67] and human dermal fibroblasts conducted by [70].”
BackgroundMethodResultInfluentialCellular 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
Erythropoietin and Wnt1 Govern Pathways of mTOR, Apaf-1, and XIAP in Inflammatory Microglia
Shang, Y., Chong, Z. Z., Wang, S., & Maiese, K. (2011) · Current Neurovascular Research · doi:10.2174/156720211798120990 · Cited by 96 · see citing works
Association of Forced Vital Capacity with the Developmental Gene NCOR2
Minelli, C., Dean, C. H., Hind, M. D., Alves, A. C., Amaral, A. F. S., Siroux, V., Huikari, V., Artigas, M. S., Evans, D. M., Loth, D. W., et al. (2016) · PLoS ONE · doi:10.1371/journal.pone.0147388 · Cited by 95 · see citing works
Hsa_circ_0000479 as a Novel Diagnostic Biomarker of Systemic Lupus Erythematosus
Guo, G., Wang, H., Ye, L., Shi, X., Yan, K., Lin, K.-M., Huang, Q., Li, B., Lin, Q., Zhu, L., et al. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.02281 · Cited by 95 · see citing works
Erythropoietin: New Directions for the Nervous System
Maiese, K., Chong, Z. Z., Shang, Y. C., & Wang, S. (2012) · International Journal of Molecular Sciences · doi:10.3390/ijms130911102 · Cited by 92 · see citing works
Wnt1, FoxO3a, and NF-κB oversee microglial integrity and activation during oxidant stress
Shang, Y., Chong, Z. Z., Hou, J., & Maiese, K. (2010) · Cellular Signalling · doi:10.1016/j.cellsig.2010.04.009 · Cited by 91 · see citing works
Deep Sequencing Reveals Novel MicroRNAs and Regulation of MicroRNA Expression during Cell Senescence
Dhahbi, J. M., Atamna, H., Boffelli, D., Magis, W., Spindler, S. R., & Martin, D. I. K. (2011) · PLoS ONE · doi:10.1371/journal.pone.0020509 · Cited by 82 · see citing works
Mao, C. D., & Byers, S. W. (2011) · Critical Reviews in Eukaryotic Gene Expression · doi:10.1615/critreveukargeneexpr.v21.i3.10 · Cited by 74 · see citing works
Qian, D., Chen, K., Deng, H., Rao, H., Huang, H.-Q., Liao, Y., Sun, X., Lü, S., Yuan, Z., Xie, D., et al. (2015) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-14-2947 · Cited by 73 · see citing works
Chong, Z. Z., Shang, Y., Hou, J., & Maiese, K. (2010) · Oxidative Medicine and Cellular Longevity · doi:10.4161/oxim.3.2.11758 · Cited by 72 · see citing works
Sklepkiewicz, P. L., Shiomi, T., Kaur, R., Sun, J., Kwon, S. H., Mercer, B. A., Bodine, P. V. N., SCHERMULY, R. T., George, I., Schulze, P. C., et al. (2015) · Circulation Heart Failure · doi:10.1161/circheartfailure.114.001274 · Cited by 70 · see citing works
Sohn, J. J., Schetter, A. J., Yfantis, H. G., Ridnour, L. A., Horikawa, I., Ma, K., Robles, A. I., Hussain, S. P., Goto, A., Bowman, E. D., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0044156 · Cited by 66 · see citing works
Self-citationWnt Signaling and Aging-Related Heart Disorders
Naito, A. T., Shiojima, I., & Komuro, I. (2010) · Circulation Research · doi:10.1161/circresaha.110.223776 · Cited by 64 · see citing works
Yıldız, G., Arslan-Ergül, A., Baǧışlar, S., Konu, Ö., Yuzugullu, H., Gürsoy-Yüzügüllü, Ö., Öztürk, N., Özen, Ç., Özdağ, H., Erdal, E., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0064016 · Cited by 60 · see citing works
Vaziri, H., Chapman, K., Guigova, A., Teichroeb, J. H., Lacher, M. D., Sternberg, H., Singeç, I., Briggs, L., Wheeler, J., Sampathkumar, J., et al. (2010) · Regenerative Medicine · doi:10.2217/rme.10.21 · Cited by 61 · see citing works
Cellular Senescence and Senotherapies in the Kidney: Current Evidence and Future Directions
Docherty, M. H., Baird, D., Hughes, J., & Ferenbach, D. A. (2020) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.00755 · Cited by 63 · see citing works
Senescence under appraisal: hopes and challenges revisited
Davan-Wetton, C. S. A., Pessolano, E., Perretti, M., & Montero‐Melendez, T. (2021) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-020-03746-x · Cited by 59 · see citing works
Xie, C., Jin, J., Lv, X., Tao, J., Wang, R., & Miao, D. (2015) · Scientific Reports · doi:10.1038/srep13975 · Cited by 58 · see citing works
RetractedGomez-Sanchez, J. A., Gomis-Coloma, C., Morenilla‐Palao, C., Peiró, G., Serra, E., Serrano, M., & Cabedo, H. (2013) · Brain · doi:10.1093/brain/awt130 · Cited by 56 · see citing works
Self-citationYu, S., Chen, M., Xu, L., Mao, E., & Sun, S. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1175490 · Cited by 55 · see citing works
A genomics approach identifies senescence‐specific gene expression regulation
Lackner, D. H., Hayashi, M. T., Cesare, A. J., & Karlseder, J. (2014) · Aging Cell · doi:10.1111/acel.12234 · Cited by 47 · see citing works
“We also identified genes with established roles in senescence (p21, p16) or with antiproliferative properties such as WNT16 (Binet et al., 2009), or BTG2 (Rouault et al., 1996).”
BackgroundJiang, Z., den Hoff, J. W. V., Torensma, R., Meng, L., & Bian, Z. (2013) · Journal of Cellular Physiology · doi:10.1002/jcp.24460 · Cited by 49 · see citing works
How to become immortal: let MEFs count the ways
Odell, A. F., Askham, J. M., Whibley, C., & Hollstein, M. (2010) · Aging · doi:10.18632/aging.100129 · Cited by 44 · see citing works
Single-Cell Analyses Identify Dysfunctional CD16+ CD8 T Cells in Smokers
Martos, S. N., Campbell, M. R., Lozoya, O. A., Wang, X., Bennett, B. D., Thompson, I. J. B., Wan, M., Pittman, G. S., & Bell, D. A. (2020) · Cell Reports Medicine · doi:10.1016/j.xcrm.2020.100054 · Cited by 42 · see citing works
Centella asiatica extracts modulate hydrogen peroxide-induced senescence in human dermal fibroblasts
Kim, Y., Cha, H. J., Nam, K. H., Yoon, Y., Lee, H., & An, S. (2011) · Experimental Dermatology · doi:10.1111/j.1600-0625.2011.01388.x · Cited by 40 · see citing works
Marthandan, S., Menzel, U., Priebe, S., Groth, M., Guthke, R., Platzer, M., Hemmerich, P., Kaether, C., & Diekmann, S. (2016) · Biological Research · doi:10.1186/s40659-016-0095-2 · Cited by 39 · see citing works
p53 governs telomere regulation feedback too, via TRF2
Horikawa, I., Fujita, K., & Harris, C. C. (2011) · Aging · doi:10.18632/aging.100271 · Cited by 38 · see citing works
Self-citationChen, L., Zhang, Y., Zhang, Z., Huang, T., & Cai, Y. (2018) · Molecular Therapy — Methods & Clinical Development · doi:10.1016/j.omtm.2018.06.007 · Cited by 36 · see citing works
Soto-Gamez, A., Wang, Y., Zhou, X., Seras, L., Quax, W. J., & Demaria, M. (2021) · Cancer Letters · doi:10.1016/j.canlet.2021.10.038 · Cited by 33 · see citing works
TET2-Dependent Hydroxymethylome Plasticity Reduces Melanoma Initiation and Progression
Bonvin, E., Radaelli, E., Bizet, M., Luciani, F., Calonne, E., Putmans, P., Nittner, D., Singh, N. K., Santagostino, S. F., Petit, V., et al. (2018) · Cancer Research · doi:10.1158/0008-5472.can-18-1214 · Cited by 30 · see citing works
Wnt16 Attenuates TGFβ-Induced Chondrogenic Transformation in Vascular Smooth Muscle
Beazley, K. E., Nurminsky, D. I., Lima, F., Gandhi, C., & Nurminskaya, M. V. (2015) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.114.304393 · Cited by 30 · see citing works
Treatment-induced secretion of WNT16B promotes tumor growth and acquired resistance to chemotherapy
Johnson, L., Price, D. K., & Figg, W. D. (2013) · Cancer Biology & Therapy · doi:10.4161/cbt.22636 · Cited by 29 · see citing works
Triptolide inhibits tumor growth by induction of cellular senescence
Li, R., Zhang, X., Tian, X., Shen, C., Zhang, Q., Zhang, Y., Wang, Z., Wang, F., & Tao, Y. (2016) · Oncology Reports · doi:10.3892/or.2016.5258 · Cited by 29 · see citing works
Jeoung, J. Y., Nam, H. Y., Kwak, J., Jin, H. J., Lee, H. J., Lee, B. W., Baek, J. H., Eom, J. S., Chang, E., Shin, D., et al. (2014) · Stem Cells and Development · doi:10.1089/scd.2014.0273 · Cited by 29 · see citing works
Hormetic effect of rotenone in primary human fibroblasts
Marthandan, S., Priebe, S., Groth, M., Guthke, R., Platzer, M., Hemmerich, P. H., & Diekmann, S. (2015) · Immunity & Ageing · doi:10.1186/s12979-015-0038-8 · Cited by 26 · see citing works
Tseligka, E. D., Rova, A., Amanatiadou, E. P., Calabrese, G., Tsibouklis, J., Fatouros, D. G., & Vizirianakis, I. S. (2016) · Pharmaceutical Research · doi:10.1007/s11095-016-1930-4 · Cited by 25 · see citing works
Shen, C., Kang, Y., Zhao, M., He, Y., Cui, D., Fu, Y., Yang, L., & Gou, L. (2014) · International Journal of Molecular Sciences · doi:10.3390/ijms150712928 · Cited by 24 · see citing works
A synthetic formulation, Dhanwantharam kashaya, delays senescence in stem cells
Warrier, S. R., Haridas, N., Balasubramanian, S., Jalisatgi, A., Bhonde, R. R., & Dharmarajan, A. (2013) · Cell Proliferation · doi:10.1111/cpr.12026 · Cited by 24 · see citing works
Mavrogonatou, E., Papadopoulou, A., Fotopoulou, A., Tsimelis, S., Bassiony, H., YIACOUMETTIS, A. M., Panagiotou, P. N., Pratsinis, H., & Kletsas, D. (2021) · Cancers · doi:10.3390/cancers13081987 · Cited by 23 · see citing works
Involvement of Wnt signaling in the injury of murine mesenchymal stem cells exposed to X-radiation
Su, W., Chen, Y., Zeng, W., Liu, W., & Hanying, S. (2012) · International Journal of Radiation Biology · doi:10.3109/09553002.2012.703362 · Cited by 20 · see citing works
Napolitano, M. A., Comegna, M., Succoio, M., Leggiero, E., Pastore, L., Faraonio, R., Cimino, F., & Passaro, F. (2014) · PLoS ONE · doi:10.1371/journal.pone.0098669 · Cited by 20 · see citing works
Circular RNAs: Potential biomarkers and therapeutic targets for autoimmune diseases
Zhao, R. R., Zhang, W., & Fan, X. (2023) · Heliyon · doi:10.1016/j.heliyon.2023.e23694 · Cited by 18 · see citing works
Trayssac, M., Clarke, C. J., Stith, J. L., Snider, J. M., Newen, N., Gault, C. R., Hannun, Y. A., & Obeid, L. M. (2021) · Cell Death and Disease · doi:10.1038/s41419-020-03281-4 · Cited by 18 · see citing works
Mao, R., Wang, Y., Wang, F., Zhou, L., Yan, S., Lu, S., Shi, W., & Zhang, Y. (2022) · Frontiers in Genetics · doi:10.3389/fgene.2022.881051 · Cited by 16 · see citing works
Progeria and Aging—Omics Based Comparative Analysis
Caliskan, A., Crouch, S. A. W., Giddins, S., Dandekar, T., & Dangwal, S. (2022) · Biomedicines · doi:10.3390/biomedicines10102440 · Cited by 15 · see citing works
Cell Sorting of Young and Senescent Cells
Hewitt, G., von Zglinicki, T., & Passos, J. F. (2013) · Methods in molecular biology · doi:10.1007/978-1-62703-556-9_4 · Cited by 12 · see citing works
Schneider, A. J., Moore, R. W., Branam, A. M., Abler, L. L., Keil, K. P., Mehta, V., Vezina, C. M., & Peterson, R. E. (2014) · Toxicological Sciences · doi:10.1093/toxsci/kfu116 · Cited by 10 · see citing works
Schmid, D., Zeis, T., Sobrio, M., & Schaeren‐Wiemers, N. (2014) · ASN NEURO · doi:10.1177/1759091414548916 · Cited by 9 · see citing works
A transcriptomic analysis of dental pulp stem cell senescence in vitro
Xu, J., Hu, M., Liu, L., Xu, X., Xu, L., & Song, Y. (2024) · BioMedical Engineering OnLine · doi:10.1186/s12938-024-01298-w · Cited by 7 · see citing works
Recent Developments in Small-Molecule Fluorescent Probes for Cellular Senescence
Park, J. L., Lee, Y., & Park, J. (2024) · Chemosensors · doi:10.3390/chemosensors12070141 · Cited by 6 · see citing works
Back to Immortality: The Restoration of Embryonic Telomere Length During Induced Pluripotency
West, M. D., & Vaziri, H. (2010) · Regenerative Medicine · doi:10.2217/rme.10.51 · Cited by 6 · see citing works
Freyter, B. M., Al‐razaq, M. A. A., Hecht, M., Rübe, C., & Rübe, C. E. (2024) · Genes · doi:10.3390/genes15070851 · Cited by 5 · see citing works
Enhanced osteointegration of implants in aged rats via a stem cell pool aging reversion strategy.
Li, X., Luo, X., He, Y., Zhou, B., Xu, K., Huang, Q., Jiang, X., Xiong, H., Liu, X.-Z., Liu, S.-P., et al. (2025) · Biomaterials · doi:10.1016/j.biomaterials.2025.123604 · Cited by 4 · see citing works
Cellular Senescence and Stem Cell Niche
Krause, A., Conboy, M. J., & Conboy, I. M. (2017) · Elsevier eBooks · doi:10.1016/b978-0-12-802734-9.00012-3 · Cited by 4 · see citing works
Cellular senescence, a novel therapeutic target for mesenchymal stem cells in acute kidney injury
Zhao, L., Hu, C., Han, F., Chen, D., Ma, Y., Wang, J., & Chen, J. (2020) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.16163 · Cited by 4 · see citing works
CYP2S1 Knockout Promotes Intestinal Tumor Growth in APCMin/+ Mice and Its Clinical Significance
Du, Y., Kuang, Y., Meng, X., Zheng, B., Chen, Q., Qian, Y., & Li, J. (2025) · Journal of Cancer · doi:10.7150/jca.111574 · Cited by 3 · see citing works
Standard of care drugs do not modulate activity of senescent primary human lung fibroblasts
Badaro‐Garcia, S., Hohmann, M. S., Coelho, A. L., Verri, W. A., Jr., & Hogaboam, C. M. (2023) · Scientific Reports · doi:10.1038/s41598-023-30844-0 · Cited by 3 · see citing works
Molecular Targets of Resveratrol in Carcinogenesis
Baek, S. J., & Whitlock, N. C. (2011) · Evidence-based anticancer complementary and alternative medicine · doi:10.1007/978-94-007-0526-5_15 · Cited by 3 · see citing works
Williamson, M., & Clements, W. K. (2024) · Differentiation · doi:10.1016/j.diff.2024.100833 · Cited by 2 · see citing works
The quest to define senescence
Esterly, A. T., & Zapata, H. J. (2024) · Frontiers in Genetics · doi:10.3389/fgene.2024.1396535 · Cited by 2 · see citing works
Xie, L., Huang, Y., Zhong, J., Wei, H., Chen, S., Jiang, K., Li, S., & Qin, X. Y. (2019) · AIDS Research and Human Retroviruses · doi:10.1089/aid.2019.0038 · Cited by 2 · see citing works
Swanson, E. C. (2014) · The Journal of the American Medical Association (JAMA) Network (American Medical Association) · doi:10.13028/m2k30f · Cited by 1 · see citing works
Wu, T., Xia, J., Shao, Y., Yang, J., Zou, C., Wang, J., & Sun, G. (2025) · Journal of Future Foods · doi:10.1016/j.jfutfo.2025.05.006 · Cited by 1 · see citing works
Harrod, C. K., Hernandez, B. Y., Yates, C., & Harrod, R. (2025) · Journal of Experimental Pharmacology · doi:10.2147/jep.s546622 · Cited by 1 · see citing works
Martos, S. N., Campbell, M. R., Lozoya, O. A., Bennett, B. D., Thompson, I. J. B., Wan, M., Pittman, G. S., & Bell, D. A. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/783126 · Cited by 1 · see citing works
(2019) · BioFactors · doi:10.1002/biof.1589 · Cited by 1 · see citing works
RetractedCaveolar Vesicles in Cellular Senescence
Wheaton, K. (2012) · InTech eBooks · doi:10.5772/31976
Binet, R., Ythier, D., Robles, A. I., Collado, M., Larrieu, D., Brambilla, E. M., Brambilla, C., Serrano, M., Harris, C. C., & Pedeux, R. (2010) · Bulletin du Cancer · doi:10.1016/s0007-4551(15)31172-3
Self-citationIdentification of Novel Molecular Targets of Resveratrol in Colorectal Carcinogenesis
Whitlock, N. C. (2011)
WNT16 in Chondrocyte Biology and Lineage Determination
Thomas, B. L. (2015)
Biomarkers From Systems Biology and “Omics” Studies
Yan, Q. (2017) · Elsevier eBooks · doi:10.1016/b978-0-12-804328-8.00006-1
Aging and Age-Associated Diseases
Yan, Q. (2017) · Elsevier eBooks · doi:10.1016/b978-0-12-804328-8.00012-7
Contribution of Extracellular Vesicles to Cancer Initiation through Cellular Senescence during Aging
Tominaga, N. (2018) · Cancer Studies · doi:10.31532/cancerstud.1.1.006
Menyhert, L. D., & Tejeda, M. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.03.05.978080
Effects of anti-fibrotic standard of care drugs on senescent human lung fibroblastsPreprint
Garcia, S. B., Hohmann, M. S., Coelho, A. L., Verri, W. A., Jr., & Hogaboam, C. M. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.05.06.490939
Menyhert, L. D., & Tejeda, M. (2025) · Developments in Health Sciences · doi:10.1556/2066.2024.00066
- Authors
- Binet, R., Ythier, D., Robles, A. I., Collado, M., Larrieu, D., Fonti, C., Brambilla, E., Brambilla, C., Serrano, M., Harris, C. C., & Pedeux, R.
- Affiliations
- Inserm (FR)
- Corresponding author
- Pedeux, Rémy
- ORCID
- Venue
- Cancer Research
- Published
- 2009-12-14
- Volume
- 69
- Issue
- 24
- Pages
- 9183-9191
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- PMC
- PMC7439003
- OpenAlex
- W2123104757
- Cited by
- 101
- References
- 43
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 5 · 2023: 3 · 2022: 3 · 2021: 4 · 2020: 7 · 2019: 6 · 2018: 3 · 2017: 5 · 2016: 9 · 2015: 9 · 2014: 10 · 2013: 8 · 2012: 6
- FWCI
- 5.10
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Cancer Institute (Z01BC005794)
- 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, replicative senescence, stress-induced premature senescence, oncogene-induced senescence, p53, p21, PI3K/Akt signaling, secreted factors, fibroblasts, tumor suppression, senescence-associated secretory phenotype
- MeSH terms
- Phosphoinositide-3 Kinase Inhibitors, Chromones, Enzyme Inhibitors, Fibroblasts, Humans, Morpholines, Transcription, Genetic, Transfection, Tumor Suppressor Protein p53, Cellular Senescence, Phosphatidylinositol 3-Kinases, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, RNA, Small Interfering, Cyclin-Dependent Kinase Inhibitor p21, Proto-Oncogene Proteins c-akt, Wnt Proteins
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
