The DOI matches its Crossref record; 31 of the 31 references it cites were found in a registry or an index.
BRAFE600-associated senescence-like cell cycle arrest of human naevi
Open accessAbstract
Most normal mammalian cells have a finite lifespan, thought to constitute a protective mechanism against unlimited proliferation. This phenomenon, called senescence, is driven by telomere attrition, which triggers the induction of tumour suppressors including p16(INK4a) (ref. 5). In cultured cells, senescence can be elicited prematurely by oncogenes; however, whether such oncogene-induced senescence represents a physiological process has long been debated. Human naevi (moles) are benign tumours of melanocytes that frequently harbour oncogenic mutations (predominantly V600E, where valine is substituted for glutamic acid) in BRAF, a protein kinase and downstream effector of Ras. Nonetheless, naevi typically remain in a growth-arrested state for decades and only rarely progress into malignancy (melanoma). This raises the question of whether naevi undergo BRAF(V600E)-induced senescence. Here we show that sustained BRAF(V600E) expression in human melanocytes induces cell cycle arrest, which is accompanied by the induction of both p16(INK4a) and senescence-associated acidic beta-galactosidase (SA-beta-Gal) activity, a commonly used senescence marker. Validating these results in vivo, congenital naevi are invariably positive for SA-beta-Gal, demonstrating the presence of this classical senescence-associated marker in a largely growth-arrested, neoplastic human lesion. In growth-arrested melanocytes, both in vitro and in situ, we observed a marked mosaic induction of p16(INK4a), suggesting that factors other than p16(INK4a) contribute to protection against BRAF(V600E)-driven proliferation. Naevi do not appear to suffer from telomere attrition, arguing in favour of an active oncogene-driven senescence process, rather than a loss of replicative potential. Thus, both in vitro and in vivo, BRAF(V600E)-expressing melanocytes display classical hallmarks of senescence, suggesting that oncogene-induced senescence represents a genuine protective physiological process.
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 source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Lastly, in mice and humans, a senescence response to strong mitogenic signals, such as those delivered by certain oncogenes, prevents premalignant lesions from progressing to malignant cancers [ 16 – 19 ].”
From Senescence-Associated Secretory Phenotypes Reveal Cell-Nonautonomous Functions of Oncogenic RAS and the p53 Tumor Suppressor (2008) · cites this paper as [18]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Additionally, the BRAF oncogenic mutation found in more than half of all malignant cutaneous melanomas is commonly found also in non-malignant nevi, where it causes oncogene-induced senescence exemplified by high levels of CDKN2A and SA-β-gal expression225–227.”
From SenNet recommendations for detecting senescent cells in different tissues (2024) · cites this paper as [225]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Mouse models of melanoma and human nevi (both oncogene driven) show accumulation of SA-β-gal+–CDKN2A+ foci224,225.”
From SenNet recommendations for detecting senescent cells in different tissues (2024) · cites this paper as [225]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“This type of oncogene-induced senescence (OIS) is frequently observed in premalignant and benign tumour tissues [37 -39] but not in advanced malignant tumours, where cancer cells have already bypassed senescence.”
From The role of cellular senescence and SASP in tumour microenvironment (2023) · cites this paper as [37]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Hallmarks of senescent cells were subsequently identified in dermal premalignant lesions, specifically human melanocytic naevi 81,82 .”
From Senescence and cancer — role and therapeutic opportunities (2022) · cites this paper as [81]
The cited source says what the claim attributes to it.
In the citing paper
“Studies in various mouse models, supported by correlative evidence from human- derived tissue samples, have underscored the tumour- suppressive role of OIS 81,120-123 .”
From Senescence and cancer — role and therapeutic opportunities (2022) · cites this paper as [81]
In the citing paper
“Oncogene-induced senescence protects against tumor initiation 34–37.”
From Cardiac glycosides are broad-spectrum senolytics (2019) · cites this paper as [35]
In the citing paper
“OIS is a powerful tumor suppressor mechanism 34–37.”
From Cardiac glycosides are broad-spectrum senolytics (2019) · cites this paper as [35]
In the citing paper
“in vitro experiments showed that cells that lack functional p53 or overexpress the H3K9me3 demethylase JMJD2c46,50 — which therefore cannot enter senescence in response to pro-senescent oncogenes such as Ras-G12V or Braf-V600E46,51 — also failed to enter VIS and lacked a SASP upon infection with SARS-CoV-2 (ref.28).”
From COVID-19 and cellular senescence (2023) · cites this paper as [51]
In the citing paper
“Studies have demonstrated high levels of senescence in premalignant lesions and lower levels in invasive disease, suggesting a role for senescence in blocking malignant progression [2,31,32].”
From Senescence and Cancer: A Review of Clinical Implications of Senescence and Senotherapies (2020) · cites this paper as [32]
In the citing paper
“human melanocytic naevi (an OIS model), remain non-proliferative for decades without transformation into malignant melanoma 25”
From Inside and out: the activities of senescence in cancer (2014) · cites this paper as [25]
In the citing paper
“This is a seminal study that identified OIS of human melanocytic naevi.”
From Inside and out: the activities of senescence in cancer (2014) · cites this paper as [25]
In the citing paper
“Senescence markers are detected in premalignant tumor lesions but not at later stages of tumor development [17,18,19].”
From Mechanisms and Regulation of Cellular Senescence (2021) · cites this paper as [19]
In the citing paper
“Benign melanocytic lesions, which are melanoma precursors in humans, express high p16 and are an in vivo example of OIS [19,55].”
From Mechanisms and Regulation of Cellular Senescence (2021) · cites this paper as [19]
In the citing paper
“Indeed, such telomeres are not visibly shorter than functional telomeres [114] in human melanocytic nevi with frequent BRAF mutations, a typical OIS feature in vivo [19].”
From Mechanisms and Regulation of Cellular Senescence (2021) · cites this paper as [19]
In the citing paper
“Indeed, its locus is more commonly deleted or silenced than mutated in melanoma, the more malignant later stage of disease [19,55].”
From Mechanisms and Regulation of Cellular Senescence (2021) · cites this paper as [19]
In the citing paper
“For example, N-RAS- or B-RAF-activating mutations are commonly found in benign melanocytic nevi that show features of senescence, such as elevated p16 levels, but that do not express appreciable levels of ARF or p53 [19,55].”
From Mechanisms and Regulation of Cellular Senescence (2021) · cites this paper as [19]
In the citing paper
“In humans, Ras activation appears to induce only p16 [19,127].”
From Mechanisms and Regulation of Cellular Senescence (2021) · cites this paper as [19]
In the citing paper
“senescence occurs during the formation of benign cutaneous melanocytic nevi that express an oncogenic form of BRAF [19].”
From Mechanisms and Regulation of Cellular Senescence (2021) · cites this paper as [19]
In the citing paper
“Importantly, this work also provided evidence for the occurrence of 4N senescent cells in human melanocyte naevi, the first in vivo senescence model, 94 suggesting that the G2 exit program has a more general role in senescence.”
From Senescence from G2 arrest, revisited (2015) · cites this paper as [94]
In the citing paper
“The acronym oncogene-induced senescence (OIS) was coined following the demonstration that the aberrant activation of oncogenes (e.g., Ras, BRAF V600E, and c-Myc) or loss of tumor suppressor genes (e.g., PTEN) temporarily arrests a large variety of tumors in a pre-malignant state 180-183 (Figure 3B).”
From Meta-hallmarks of aging and cancer (2023) · cites this paper as [182]
In the citing paper
“BRAFV600E mutation alone is often insufficient to drive malignant transformation of melanocytes24.”
From Mechanisms and prevention of UV‐induced melanoma (2018) · cites this paper as [24]
In the citing paper
“For example, developmental senescent cells express p21WAF1/Cip1 but not p16INK4a9,10, while the reverse is observed in melanocytic nevi36,37.”
From Algorithmic assessment of cellular senescence in experimental and clinical specimens (2021) · cites this paper as [36]
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
Mutations of the BRAF gene in human cancer
Davies, H., Bignell, G. R., Cox, C., Stephens, P., Edkins, S., Clegg, S., Teague, J., Woffendin, H., Garnett, M. J., Bottomley, W., et al. (2002) · Nature · doi:10.1038/nature00766 · Cited by 10,674
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
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
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
A cell cycle regulator potentially involved in genesis of many tumor types
Kamb, A., Gruis, N. A., Weaver-Feldhaus, J., Liu, Q., Harshman, K., Tavtigian, S. V., Stockert, E., Day, R. S., Johnson, B. E., & Skolnick, M. H. (1994) · Science · doi:10.1126/science.8153634 · Cited by 2,751
Senescent cells, tumor suppression, and organismal aging: good citizens, bad neighbors
Campisi, J. (2005) · Cell · doi:10.1016/j.cell.2005.02.003 · Cited by 2,379
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
High frequency of BRAF mutations in nevi
Pollock, P. M., Harper, U. L., Hansen, K. S., Yudt, L. M., Stark, M., Robbins, C. M., Moses, T. Y., Hostetter, G., Wagner, U., Kakareka, J., et al. (2003) · Nature Genetics · doi:10.1038/ng1054 · Cited by 1,730
Reversal of human cellular senescence: roles of the p53 and p16 pathways
Beauséjour, C. M., Krtolica, A., Galimi, F., Narita, M., Lowe, S. W., Yaswen, P., & Campisi, J. (2003) · The EMBO Journal · doi:10.1093/emboj/cdg417 · Cited by 1,457
Lowe, S. W., Cepero, E., & Evan, G. I. (2004) · Nature · doi:10.1038/nature03098 · Cited by 1,374
Flagged first, then by citations
Research works printed but not linked: 1
- Peeper, D. S. & Mooi, W. J. Pathogenesis of melanocytic naevi: growth arrest linked with cellular senescence? Histopathology 41, S139–S143 (2002)
Cited by
Sorted by citations
Items 301–400 of 1,009
Pathogenesis of Langerhans Cell Histiocytosis
Badalian‐Very, G., Vergilio, J., Fleming, M. D., & Rollins, B. J. (2012) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev-pathol-020712-163959 · Cited by 168
Inamura, K. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19041259 · Cited by 168
MITF and UV responses in skin: From pigmentation to addiction
Nguyen, N. T., & Fisher, D. E. (2018) · Pigment Cell & Melanoma Research · doi:10.1111/pcmr.12726 · Cited by 168
The genome and epigenome of malignant melanoma
Dahl, C., & Guldberg, P. (2007) · Apmis · doi:10.1111/j.1600-0463.2007.apm_855.xml.x · Cited by 165
Ueda, Y., & Richmond, A. J. (2006) · Pigment Cell Research · doi:10.1111/j.1600-0749.2006.00304.x · Cited by 164
KRAS and BRAF: drug targets and predictive biomarkers
Vakiani, E., & Solit, D. B. (2010) · The Journal of Pathology · doi:10.1002/path.2796 · Cited by 164
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
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
HIF1α delays premature senescence through the activation of MIFPreprint
Welford, S. M., Bedogni, B., Gradin, K., Poellinger, L., Powell, M. B., & Giaccia, A. J. (2006) · Genes & Development · doi:10.1101/gad.1471106 · Cited by 163
Rai, T. S., Cole, J. J., Nelson, D. M., Dikovskaya, D., Faller, W. J., Vizioli, M. G., Hewitt, R. N., Anannya, O., McBryan, T., Manoharan, I., et al. (2014) · Genes & Development · doi:10.1101/gad.247528.114 · Cited by 162
Muñoz, 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
The role of cellular senescence in skin aging and age-related skin pathologies
Chin, T., Lee, X. E., Ng, P. Y., Lee, Y., & Dreesen, O. (2023) · Frontiers in Physiology · doi:10.3389/fphys.2023.1297637 · Cited by 164
Systems biology of ageing and longevity
Kirkwood, T. B. L. (2010) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2010.0275 · Cited by 162
Telomerase, senescence and ageing
Shawi, M., & Autexier, C. (2008) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2007.11.007 · Cited by 160
Aging by epigenetics—A consequence of chromatin damage?
Sedivy, J. M., Gowrishankar, B., & Adams, P. D. (2008) · Experimental Cell Research · doi:10.1016/j.yexcr.2008.02.023 · Cited by 159
Proteasomal and Genetic Inactivation of the NF1 Tumor Suppressor in Gliomagenesis
McGillicuddy, L. T., Longo, J. F., Hollstein, P. E., Kubek, S., Beroukhim, R., Raedt, T. D., Johnson, B. W., Williams, S. M. G., Nghiemphu, P. L., Liau, L. M., et al. (2009) · Cancer Cell · doi:10.1016/j.ccr.2009.05.009 · Cited by 158
Tbx3 Represses E-Cadherin Expression and Enhances Melanoma Invasiveness
Rodriguez, M., Aladowicz, E., Lanfrancone, L., & Goding, C. R. (2008) · Cancer Research · doi:10.1158/0008-5472.can-08-0301 · Cited by 157
MLL1 is essential for the senescence-associated secretory phenotype
Capell, B. C., Drake, A. M., Zhu, J., Shah, P. P., Dou, Z., Dorsey, J., Simola, D. F., Donahue, G., Sammons, M., Rai, T. S., et al. (2016) · Genes & Development · doi:10.1101/gad.271882.115 · Cited by 156
Yu, Y., Schleich, K., Yue, B., Ji, S., Lohneis, P., Kemper, K., Silvis, M. R., Qutob, N., van Rooijen, E., Werner-Klein, M., et al. (2018) · Cancer Cell · doi:10.1016/j.ccell.2018.01.002 · Cited by 156
Self-citationThe miR-17-92 Cluster of MicroRNAs Confers Tumorigenicity by Inhibiting Oncogene-Induced Senescence
Hong, L., Lai, M., Chen, M. S., Xie, C., Liao, R., Kang, Y. J., Xiao, C., Hu, W.-Y., Han, J., & Sun, P. (2010) · Cancer Research · doi:10.1158/0008-5472.can-10-1938 · Cited by 156
Gowrishankar, B., Somaiah, N., Zhang, R., Tang, Y., Hoffmann, J., Andrake, M., Ceulemans, H., Schultz, D., Marmorstein, R., & Adams, P. D. (2008) · Molecular and Cellular Biology · doi:10.1128/mcb.01047-08 · Cited by 156
Oncogene-induced senescence results in marked metabolic and bioenergetic alterations
Quijano, C., Cao, L., Fergusson, M. M., Romero, H., Liu, J., Gutkind, S., Rovira, I. I., Mohney, R. P., Karoly, E. D., & Finkel, T. (2012) · Cell Cycle · doi:10.4161/cc.19800 · Cited by 155
Mitochondria Damage Checkpoint, Aging, and Cancer
Singh, K. K. (2006) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1354.022 · Cited by 155
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
Modelling cancer in human skin tissue
Khavari, P. A. (2006) · Nature reviews. Cancer · doi:10.1038/nrc1838 · Cited by 154
Genetic insights into OXPHOS defect and its role in cancer
Chandra, D., & Singh, K. K. (2010) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2010.10.023 · Cited by 155
Yoshida, A., Lee, E. K., & Diehl, J. A. (2016) · Cancer Research · doi:10.1158/0008-5472.can-15-2931 · Cited by 153
COVID-19 and cellular senescence
Schmitt, C. A., Tchkonia, T., Niedernhofer, L. J., Robbins, P. D., Kirkland, J. L., & Lee, S. (2023) · Nature Reviews Immunology · doi:10.1038/s41577-022-00785-2 · Cited by 153
Extracellular matrix alterations in senescent cells and their significance in tissue homeostasis
Mavrogonatou, E., Pratsinis, H., Papadopoulou, A., Karamanos, N. K., & Kletsas, D. (2019) · Matrix Biology · doi:10.1016/j.matbio.2017.10.004 · Cited by 153
Cellular senescence and chromatin structure
Funayama, R., & Ishikawa, F. (2007) · Chromosoma · doi:10.1007/s00412-007-0115-7 · Cited by 153
Selvam, S. P., Palma, R. M. D., Oaks, J. J., Oleinik, N. V., Peterson, Y. K., Stahelin, R. V., Skordalakes, E., Ponnusamy, S., Garrett-Mayer, E. S., Smith, C. D., et al. (2015) · Science Signaling · doi:10.1126/scisignal.aaa4998 · Cited by 155
Inflammatory signaling and cellular senescence
Ren, J., Pan, J., Lu, Y.-P., Sun, P., & Han, J. (2008) · Cellular Signalling · doi:10.1016/j.cellsig.2008.10.011 · Cited by 153
Narita, M., & Lowe, S. W. (2005) · Nature Medicine · doi:10.1038/nm0905-920 · Cited by 153
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
Melanoma: From Melanocyte to Genetic Alterations and Clinical Options
Bertolotto, C. (2013) · Scientifica · doi:10.1155/2013/635203 · Cited by 152
Stem cells, senescence, neosis and self-renewal in cancer.
Rajaraman, R., Guernsey, D. L., Rajaraman, M. M., & Rajaraman, S. R. (2006) · Cancer Cell International · doi:10.1186/1475-2867-6-25 · Cited by 152
Mitochondrial regulation of epigenetics and its role in human diseases
Minocherhomji, S., Tollefsbol, T. O., & Singh, K. K. (2012) · Epigenetics · doi:10.4161/epi.19547 · Cited by 151
Plentz, R. R., Park, Y. N., Lechel, A., Kim, H., Nellessen, F., Langkopf, B. H. E., Wilkens, L., Destro, A., Fiamengo, B., Manns, M. P., et al. (2007) · Hepatology · doi:10.1002/hep.21552 · Cited by 149
p21 Cip1 restrains pituitary tumor growth
Chesnokova, V., Zonis, S., Kovács, K., Ben-Shlomo, A., Wawrowsky, K., Bannykh, S., & Melmed, S. K. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0804810105 · Cited by 149
Cao, L., Kim, S., Xiao, C., Wang, R., Coumoul, X., Wang, X., Li, W. M., Xu, X. L., Soto, J. A. D., Takai, H., et al. (2006) · The EMBO Journal · doi:10.1038/sj.emboj.7601115 · Cited by 150
Sharpless, N. E., & DePinho, R. A. (2005) · Nature · doi:10.1038/436636a · Cited by 149
The roles of microphthalmia-associated transcription factor and pigmentation in melanoma
Hsiao, J. J., & Fisher, D. E. (2014) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2014.07.019 · Cited by 148
The PTEN-AKT3 signaling cascade as a therapeutic target in melanoma
Madhunapantula, S. V., & Robertson, G. P. (2009) · Pigment Cell & Melanoma Research · doi:10.1111/j.1755-148x.2009.00585.x · Cited by 148
Bi-allelic Loss of CDKN2A Initiates Melanoma Invasion via BRN2 Activation
Zeng, H., Jorapur, A., Shain, A. H., Lang, U. E., Torres, R., Zhang, Y., McNeal, A. S., Botton, T., Lin, J., Donne, M. L., et al. (2018) · Cancer Cell · doi:10.1016/j.ccell.2018.05.014 · Cited by 148
Epigenetic clock analyses of cellular senescence and ageing.
Lowe, D., Horvath, S., & Raj, K. (2016) · Oncotarget · doi:10.18632/oncotarget.7383 · Cited by 147
ARF functions as a melanoma tumor suppressor by inducing p53-independent senescence
Ha, L., Ichikawa, T., Anver, M. R., Dickins, R. A., Lowe, S. W., Sharpless, N. E., Krimpenfort, P., DePinho, R. A., Bennett, D. C., Sviderskaya, E. V., et al. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0611638104 · Cited by 147
Biology and Clinical Relevance of the Micropthalmia Family of Transcription Factors in Human Cancer
Haq, R., & Fisher, D. E. (2011) · Journal of Clinical Oncology · doi:10.1200/jco.2010.32.6223 · Cited by 146
Hinoue, T., Weisenberger, D. J., Pan, F., Campan, M., Kim, M.-J., Young, J. P., Whitehall, V., Leggett, B., & Laird, P. W. (2009) · PLoS ONE · doi:10.1371/journal.pone.0008357 · Cited by 146
Velho, S., Moutinho, C., Cirnes, L., Albuquerque, C. M., Hamelin, R., Schmitt, F. C., Carneiro, F., Oliveíra, C., & Seruca, R. (2008) · BMC Cancer · doi:10.1186/1471-2407-8-255 · Cited by 145
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
MC1R Is a Potent Regulator of PTEN after UV Exposure in Melanocytes
Cao, J., Wan, L., Hacker, E., Dai, X., Lenna, S., Jimenez-Cervantes, C., Wang, Y., Leslie, N. R., Xu, G. X., Widlund, H. R., et al. (2013) · Molecular Cell · doi:10.1016/j.molcel.2013.08.010 · Cited by 144
Carragher, L. A. S., Snell, K. R., Giblett, S. M., Aldridge, V. S. S., Patel, B., Cook, S. J., Winton, D. J., Marais, R., & Pritchard, C. A. (2010) · EMBO Molecular Medicine · doi:10.1002/emmm.201000099 · Cited by 144
The role of cellular senescence and SASP in tumour microenvironment
Takasugi, M., Yoshida, Y., Hara, E., & Ohtani, N. (2023) · The FEBS Journal · doi:10.1111/febs.16381 · Cited by 144
Molecular Pathogenesis of Cutaneous Melanocytic Neoplasms
Ibrahim, N., & Haluska, F. G. (2008) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev.pathol.3.121806.151541 · Cited by 144
Derepression 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
Colorimetric Detection of Senescence-Associated β Galactosidase
Itahana, K., Itahana, Y., & Dimri, G. P. (2012) · Methods in molecular biology · doi:10.1007/978-1-62703-239-1_8 · Cited by 142
Understanding Melanoma Signaling Networks as the Basis for Molecular Targeted Therapy
Smalley, K. S. M. (2009) · Journal of Investigative Dermatology · doi:10.1038/jid.2009.177 · Cited by 142
Telomeric 8-oxo-guanine drives rapid premature senescence in the absence of telomere shortening
Barnes, R. P., Rosa, M. D., Thosar, S. A., Detwiler, A. C., Roginskaya, V. Y., Houten, B. V., Bruchez, M. P., Stewart-Ornstein, J., & Opresko, P. L. (2022) · Nature Structural & Molecular Biology · doi:10.1038/s41594-022-00790-y · Cited by 142
Tien, A., Tsai, H., Molofsky, A. V., McMahon, M., Foo, L. C., Kaul, A., Dougherty, J. D., Heintz, N., Gutmann, D. H., Barres, B. A., et al. (2012) · Development · doi:10.1242/dev.077214 · Cited by 142
Harnessing the complexity of DNA-damage response pathways to improve cancer treatment outcomes
Al‐Ejeh, F., Kumar, R., Wiegmans, A. P., Lakhani, S. R., Brown, M. P., & Khanna, K. K. (2010) · Oncogene · doi:10.1038/onc.2010.407 · Cited by 141
Lozano-Torres, B., Estepa-Fernández, A., Rovira, M., Orzáez, M., Serrano, M., Martínez-Máñez, R., & Sancenón, F. (2019) · Nature Reviews Chemistry · doi:10.1038/s41570-019-0108-0 · Cited by 140
Hudlebusch, H. R., Santoni‐Rugiu, E., Simon, R., Ralfkiaer, E. M., Holten‐Rossing, H., Johansen, J. V., Jørgensen, M., Sauter, G., & Helin, K. (2011) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-10-1302 · Cited by 139
Melanoma: Molecular pathogenesis and emerging target therapies (Review)
Libra, M. (2009) · International Journal of Oncology · doi:10.3892/ijo_00000277 · Cited by 139
AURKB as a target in non-small cell lung cancer with acquired resistance to anti-EGFR therapy
Bertrán-Alamillo, J., Cattan, V., Schoumacher, M., Codony‐Servat, J., Giménez-Capitán, A. A., Cantero, F., Burbridge, M. F., Rodríguez, S., Teixidó, C., Roman, R. A., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-09734-5 · Cited by 139
Epigenetic Regulation of Cellular Senescence
Crouch, J. D., Shvedova, M., Thanapaul, R. J. R. S., Botchkarev, V. A., & Roh, D. S. (2022) · Cells · doi:10.3390/cells11040672 · Cited by 139
Krizhanovsky, V., Xue, W., Zender, L., Yon, M., Hernando, E., & Lowe, S. W. (2008) · Cold Spring Harbor Symposia on Quantitative Biology · doi:10.1101/sqb.2008.73.048 · Cited by 138
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
Molecular drivers of cellular metabolic reprogramming in melanoma
Abildgaard, C., & Guldberg, P. (2015) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2014.12.007 · Cited by 138
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
The Chromatin Landscape of Cellular Senescence
Criscione, S. W., Teo, Y. V., & Neretti, N. (2016) · Trends in Genetics · doi:10.1016/j.tig.2016.09.005 · Cited by 137
Oncological role of HMGA2 (Review)
Zhang, S., Mo, Q., & Wang, X. (2019) · International Journal of Oncology · doi:10.3892/ijo.2019.4856 · Cited by 137
NAKATO, N., Takata, M., Takayanagi, S., Takashima, S., Lin, J., Murata, H., Fujimoto, A., Hatta, N., & Saida, T. (2006) · Journal of Investigative Dermatology · doi:10.1038/sj.jid.5700366 · Cited by 137
Regulation of glucose metabolism by p53: Emerging new roles for the tumor suppressor
Madan, E., Gogna, R., Bhatt, M. L. B., Pati, U., Kuppusamy, P., & Mahdi, A. A. (2011) · Oncotarget · doi:10.18632/oncotarget.389 · Cited by 137
Zehavi, L., Avraham, R., Barzilai, A., Bar-Ilan, D., Navon, R., Sidi, Y., Avni, D., & Leibowitz‐Amit, R. (2012) · Molecular Cancer · doi:10.1186/1476-4598-11-44 · Cited by 137
Shojaee, S., Caeser, R., Buchner, M., Park, E., Swaminathan, S., Hurtz, C., Geng, H., Chan, L. N., Klemm, L., Hofmann, W., et al. (2015) · Cancer Cell · doi:10.1016/j.ccell.2015.05.008 · Cited by 136
Bedogni, B., & Powell, M. B. (2009) · Pigment Cell & Melanoma Research · doi:10.1111/j.1755-148x.2009.00553.x · Cited by 136
Molecular signaling and genetic pathways of senescence: Its role in tumorigenesis and aging
Zhang, H. (2006) · Journal of Cellular Physiology · doi:10.1002/jcp.20919 · Cited by 136
Targets of Raf in tumorigenesis
Niault, T., & Baccarini, M. (2010) · Carcinogenesis · doi:10.1093/carcin/bgp337 · Cited by 136
Shahbandi, A., Rao, S. G., Anderson, A. Y., Frey, W. D., Olayiwola, J. O., Ungerleider, N., & Jackson, J. G. (2020) · Cell Death and Differentiation · doi:10.1038/s41418-020-0564-6 · Cited by 135
Tasdogan, A., Sullivan, R. J., Katalinic, A., Lebbé, C., Whitaker, D., Puig, S., van de Poll-Franse, L. V., Massi, D., & Schadendorf, D. (2025) · Nature Reviews Disease Primers · doi:10.1038/s41572-025-00603-8 · Cited by 143
Colucci, M., Sarill, M., Maddalena, M., Valdata, A., Troiani, M., Massarotti, M., Bolis, M., Bressan, S., Kohl, A., Robesti, D., et al. (2025) · Cancer Cell · doi:10.1016/j.ccell.2025.05.015 · Cited by 143
CPEB regulation of human cellular senescence, energy metabolism, and p53 mRNA translation
Burns, D. M., & Richter, J. D. (2008) · Genes & Development · doi:10.1101/gad.1697808 · Cited by 134
Oncogenic NRAS Cooperates with p53 Loss to Generate Melanoma in Zebrafish
Dovey, M. C., White, R. M., & Zon, L. I. (2009) · Zebrafish · doi:10.1089/zeb.2009.0606 · Cited by 134
Tameire, F., Verginadis, I. I., & Koumenis, C. (2015) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2015.04.002 · Cited by 134
Senescent cells: Living or dying is a matter of NK cells
Antonangeli, F., Zingoni, A., Soriani, A., & Santoni, A. (2019) · Journal of Leukocyte Biology · doi:10.1002/jlb.mr0718-299r · Cited by 134
Translational control of cell growth and malignancy by the CPEBs
D’Ambrogio, A., Nagaoka, K., & Richter, J. D. (2013) · Nature reviews. Cancer · doi:10.1038/nrc3485 · Cited by 133
The Complexity of the ERK/MAP-Kinase Pathway and the Treatment of Melanoma Skin Cancer
Wellbrock, C., & Arozarena, I. (2016) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2016.00033 · Cited by 132
Zhang, H., Liao, H.-Y., Bai, D.-Y., Wang, Z., & Xie, X. (2021) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2021.112170 · Cited by 132
Loss of lamin B1 is a biomarker to quantify cellular senescence in photoaged skin
Wang, A. S., Ong, P. F., Chojnowski, A., Clavel, C., & Dreesen, O. (2017) · Scientific Reports · doi:10.1038/s41598-017-15901-9 · Cited by 131
Nassour, J., Martien, S., Martin, N., Deruy, E., Tomellini, E., Malaquin, N., Bouali, F., Sabatier, L., Wernert, N., Pinte, S., et al. (2016) · Nature Communications · doi:10.1038/ncomms10399 · Cited by 131
Overcoming resistance to BRAF inhibitors
Arozarena, I., & Wellbrock, C. (2017) · Annals of Translational Medicine · doi:10.21037/atm.2017.06.09 · Cited by 131
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
Laine, A., Sihto, H., Come, C., Rosenfeldt, M. T., Zwolinska, A., Niemelä, M., Khanna, A., Chan, E. K., Kähäri, V.-M., Kellokumpu-Lehtinen, P.-L., et al. (2013) · Cancer Discovery · doi:10.1158/2159-8290.cd-12-0292 · Cited by 130
Kumar, M., Seeger, W., & Voswinckel, R. (2014) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2013-0382ps · Cited by 131
Mechanisms and significance of therapy-induced and spontaneous senescence of cancer cells
Mikuła‐Pietrasik, J., Niklas, A. A., Uruski, P., Tykarski, A., & Książek, K. (2019) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-019-03261-8 · Cited by 131
Sakamoto, H., Shimizu, J., Horio, Y., Ueda, R., Takahashi, T., Mitsudomi, T., & Yatabe, Y. (2007) · The Journal of Pathology · doi:10.1002/path.2165 · Cited by 129
Costa, Â. M., Herrero, A., Fresno, M., Heymann, J. J., Alvarez, J. A., Cameselle‐Teijeiro, J., & García‐Rostán, G. (2007) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2007.03077.x · Cited by 129
The atypical E2F family member E2F7 couples the p53 and RB pathways during cellular senescencePreprint
Aksoy, O., Chicas, A., Zeng, T., Zhao, Z., McCurrach, M. E., Wang, X., & Lowe, S. W. (2012) · Genes & Development · doi:10.1101/gad.196238.112 · Cited by 130
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
Cytokine expression and signaling in drug-induced cellular senescence
Novakova, Z., Hubackova, S., Kosar, M., Janderova-Rossmeislova, L., Dobrovolna, J., Vasicova, P., Vancurova, M., Horejsi, Z., Hozak, P., Bartek, J., et al. (2010) · Oncogene · doi:10.1038/onc.2009.318 · Cited by 127
Metadata
- Authors
- 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.
- Affiliations
- The Netherlands Cancer Institute (NL)
- University of Michigan (US)
- Harold C. Simmons Comprehensive Cancer Center (US)
- Corresponding author
- Mooi, Wolter J.
- Peeper, Daniel S.
- Venue
- Nature
- Published
- 2005-08
- Volume
- 436
- Issue
- 7051
- Pages
- 720-724
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2150740687
- Semantic Scholar
- bfbf433cb25b4a5e054e35a6850376801a03b87d
- Cited by
- 2,160
- References
- 31
- Citations by year
- 2026: 35 · 2025: 43 · 2024: 70 · 2023: 82 · 2022: 77 · 2021: 85 · 2020: 86 · 2019: 108 · 2018: 99 · 2017: 91 · 2016: 121 · 2015: 112 · 2014: 120 · 2013: 143 · 2012: 136
- FWCI
- 66.52
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Deep Blue (University of Michigan) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Pure Amsterdam UMC (submittedVersion)
- Funders
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek
- National Institutes of Health
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Melanoma and MAPK Pathways
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Keywords
- cellular senescence, BRAF V600E mutation, melanocytes, nevi, melanoma, cell cycle arrest, senescence-associated heterochromatin foci, SUV39H1, histone methyltransferase, p16INK4a, p53, PTEN, oncogene-induced senescence, tumor suppression
- MeSH terms
- beta-Galactosidase, Cell Cycle, Cell Line, Fibroblasts, Humans, Infant, Melanocytes, Nevus, Telomere, Cellular Senescence, In Situ Hybridization, Fluorescence, Cyclin-Dependent Kinase Inhibitor p16, Proto-Oncogene Proteins B-raf, Cell Proliferation
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
