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 201–300 of 1,009
TERT promoter mutations in cancer development
Heidenreich, B., Rachakonda, P. S., Hemminki, K., & Kumar, R. (2014) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2013.11.005 · Cited by 238
Advances on Natural Polyphenols as Anticancer Agents for Skin Cancer
Sajadimajd, S., Bahramsoltani, R., Iranpanah, A., Patra, J. K., Das, G., Gouda, S., Rahimi, R., Rezaeiamiri, E., Cao, H., Giampieri, F., et al. (2019) · Pharmacological Research · doi:10.1016/j.phrs.2019.104584 · Cited by 238
Ramsey, M. R., & Sharpless, N. E. (2006) · Nature Cell Biology · doi:10.1038/ncb1106-1213 · Cited by 237
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 237
Senescence and Cancer: A Review of Clinical Implications of Senescence and Senotherapies
Wyld, L., Bellantuono, I., Tchkonia, T., Morgan, J., Turner, O., Foss, F., George, J., Danson, S., & Kirkland, J. L. (2020) · Cancers · doi:10.3390/cancers12082134 · Cited by 235
“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].”
BackgroundSenescence: a new weapon for cancer therapy
Acosta, J. C., & Gil, J. (2012) · Trends in Cell Biology · doi:10.1016/j.tcb.2011.11.006 · Cited by 235
Roads to melanoma: Key pathways and emerging players in melanoma progression and oncogenic signaling
Paluncic, J., Kovačević, Ž., Jansson, P. J., Kalinowski, D. S., Merlot, A. M., Huang, M., Lok, H. C., Sahni, S., Lane, D. J. R., & Richardson, D. R. (2016) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2016.01.025 · Cited by 236
ATP-Dependent Lon Protease Controls Tumor Bioenergetics by Reprogramming Mitochondrial Activity
Quirós, P. M., Español, Y., Acín-Pérez, R., Rodríguez, F., Bárcena, C., Watanabe, K., Calvo, E., Loureiro, M., Fernández-García, M. S., Fueyo, A., et al. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.06.018 · Cited by 233
Outgrowth of single oncogene-expressing cells from suppressive epithelial environments
Leung, C. T., & Brugge, J. S. (2012) · Nature · doi:10.1038/nature10826 · Cited by 233
Loo, T. M., Miyata, K., Tanaka, Y., & Takahashi, A. (2020) · Cancer Science · doi:10.1111/cas.14266 · Cited by 232
An integrated genomic analysis of lung cancer reveals loss of DUSP4 in EGFR-mutant tumors
Chitale, D. A., Gong, Y., Taylor, B. S., Broderick, S., Brennan, C., Somwar, R., Golas, B., Wang, L., Motoi, N., Szőke, J., et al. (2009) · Oncogene · doi:10.1038/onc.2009.135 · Cited by 232
Targeting the MAPK pathway in melanoma: Why some approaches succeed and other fail
Inamdar, G. S., Madhunapantula, S. V., & Robertson, G. P. (2010) · Biochemical Pharmacology · doi:10.1016/j.bcp.2010.04.029 · Cited by 232
Actions of human telomerase beyond telomeres
Cong, Y., & Shay, J. W. (2008) · Cell Research · doi:10.1038/cr.2008.74 · Cited by 231
Self-citationSuram, A., Kaplunov, J., Patel, P. L., Ruan, H., Cerutti, A., Boccardi, V., Fumagalli, M., Di Micco, R., Mirani, N., Gurung, R. L., et al. (2012) · The EMBO Journal · doi:10.1038/emboj.2012.132 · Cited by 227
Rad, R., Cadiñanos, J., Rad, L., Varela, I., Strong, A., Kriegl, L., Constantino‐Casas, F., Eser, S., Hieber, M., Seidler, B., et al. (2013) · Cancer Cell · doi:10.1016/j.ccr.2013.05.014 · Cited by 227
MAPK pathway activation in pilocytic astrocytoma
Jones, D., Gronych, J., Lichter, P., Witt, O., & Pfister, S. M. (2011) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-011-0898-9 · Cited by 227
Pathways and therapeutic targets in melanoma
Shtivelman, E., Davies, M. A., Hwu, P., Yang, J. C.-H., Lotem, M., Oren, M., Flaherty, K. T., & Fisher, D. E. (2014) · Oncotarget · doi:10.18632/oncotarget.1892 · Cited by 226
Mitochondrial dynamics as regulators of cancer biology
Trotta, A. P., & Chipuk, J. E. (2017) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-016-2451-3 · Cited by 226
Cold atmospheric plasma, a new strategy to induce senescence in melanoma cells
Arndt, S., Wacker, E., Li, Y., Shimizu, T., Thomas, H. M., Morfill, G. E., Karrer, S., Zimmermann, J. L., & Bosserhoff, A. (2013) · Experimental Dermatology · doi:10.1111/exd.12127 · Cited by 225
Wang, L., Leite de Oliveira, R., Wang, C., Fernandes Neto, J. M., Mainardi, S., Evers, B., Lieftink, C., Morris, B., Jochems, F., Willemsen, L., et al. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.09.085 · Cited by 224
JAK-STAT signaling in cancer: From cytokines to non-coding genome
Pěnčík, J., Pham, H. T. T., Schmoellerl, J., Javaheri, T., Schlederer, M., Čulig, Z., Merkel, O., Moriggl, R., Grebien, F., & Kenner, L. (2016) · Cytokine · doi:10.1016/j.cyto.2016.06.017 · Cited by 221
Zhuang, D., Mannava, S., Grachtchouk, V., Tang, W. H., Patil, S. B., Wawrzyniak, J. A., Berman, A. E., Giordano, T. J., Prochownik, E. V., Soengas, M. S., et al. (2008) · Oncogene · doi:10.1038/onc.2008.258 · Cited by 219
Self-citationCancer chemotherapy: insights into cellular and tumor microenvironmental mechanisms of action
Tilsed, C. M., Fisher, S. A., Nowak, A. K., Lake, R., & Lesterhuis, W. J. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.960317 · Cited by 219
Gauthier, M. L., Berman, H. K., Miller, C., Kozakeiwicz, K., Chew, K., Moore, D., Rabban, J., Chen, Y. Y., Kerlikowske, K., & Tlsty, T. D. (2007) · Cancer Cell · doi:10.1016/j.ccr.2007.10.017 · Cited by 214
Critical Functions of the Lysosome in Cancer Biology
Davidson, S. M., & Heiden, M. G. V. (2016) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-010715-103101 · Cited by 214
Kennedy, A. L., Morton, J. P., Manoharan, I., Nelson, D. M., Jamieson, N. B., Pawlikowski, J. S., McBryan, T., Doyle, B., McKay, C., Oien, K. A., et al. (2011) · Molecular Cell · doi:10.1016/j.molcel.2011.02.020 · Cited by 213
Souroullas, G. P., Jeck, W. R., Parker, J. S., Simon, J. M., Liu, J.-Y., Paulk, J., Xiong, J., Clark, K. S., Fedoriw, Y., Qi, J., et al. (2016) · Nature Medicine · doi:10.1038/nm.4092 · Cited by 212
Li, J., Spensberger, D., Ahn, J. S., Anand, S., Beer, P. A., Ghevaert, C., Chen, E., Forrai, A., Scott, L. M., Ferreira, R., et al. (2010) · Blood · doi:10.1182/blood-2009-12-259747 · Cited by 212
Xing, F., Persaud, Y., Pratilas, C. A., Taylor, B. S., Janakiraman, M., She, Q., Gallardo, H. F., Liu, C., Merghoub, T., Hefter, B., et al. (2011) · Oncogene · doi:10.1038/onc.2011.250 · Cited by 212
The journey from melanocytes to melanoma
Centeno, P. P., Pavet, V., & Marais, R. (2023) · Nature reviews. Cancer · doi:10.1038/s41568-023-00565-7 · Cited by 211
Hafner, C. M., López‐Knowles, E., Luis, N. M., Toll, A., Baselga, E., Fernandez-Casado, A., Hernandez, S. F., Ribé, A., Mentzel, T., Stoehr, R., et al. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0705218104 · Cited by 210
MicroRNAs linking inflamm-aging, cellular senescence and cancer
Olivieri, F., Rippo, M. R., Monsurrò, V., Salvioli, S., Capri, M., Procopio, A. D., & Franceschi, C. (2013) · Ageing Research Reviews · doi:10.1016/j.arr.2013.05.001 · Cited by 210
Atg7 Overcomes Senescence and Promotes Growth of Braf V600E-Driven Melanoma
Xie, X., Koh, J. Y., Price, S., White, E., & Mehnert, J. M. (2015) · Cancer Discovery · doi:10.1158/2159-8290.cd-14-1473 · Cited by 208
Immunosurveillance of senescent cells: the bright side of the senescence program
Sagiv, A., & Krizhanovsky, V. (2013) · Biogerontology · doi:10.1007/s10522-013-9473-0 · Cited by 208
How to make a melanoma: what do we know of the primary clonal events?
Bennett, D. C. (2008) · Pigment Cell & Melanoma Research · doi:10.1111/j.1755-148x.2007.00433.x · Cited by 208
BRAF Signaling and Targeted Therapies in Melanoma
Dhomen, N. S., & Marais, R. (2009) · Hematology/Oncology Clinics of North America · doi:10.1016/j.hoc.2009.04.001 · Cited by 208
Akt3 and Mutant V600EB-Raf Cooperate to Promote Early Melanoma Development
Cheung, M., Sharma, A. K., Madhunapantula, S. V., & Robertson, G. P. (2008) · Cancer Research · doi:10.1158/0008-5472.can-07-5867 · Cited by 206
Cosme‐Blanco, W., Shen, M., Lazar, A. J. F., Pathak, S., Lozano, G., Multani, A. S., & Chang, S. (2007) · The EMBO Reports · doi:10.1038/sj.embor.7400937 · Cited by 205
Cellular senescence in cancer: from mechanisms to detection
Ou, H., Hoffmann, R. J., González‐López, C., Doherty, G. J., Korkola, J. E., & Muñoz‐Espín, D. (2020) · Molecular Oncology · doi:10.1002/1878-0261.12807 · Cited by 208
Erdheim–Chester disease: A systematic review
Cives, M., Simone, V. D., Rizzo, F. M., Dicuonzo, F., Lacalamita, M. C., Ingravallo, G., Silvestris, F., & Dammacco, F. (2015) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2015.02.004 · Cited by 203
BRD7 is a candidate tumour suppressor gene required for p53 function
Drost, J., Mantovani, F., Tocco, F., Elkon, R., Comel, A., Holstege, H. H., Kerkhoven, R. M., Jonkers, J., Voorhoeve, P. M., Agami, R., et al. (2010) · Nature Cell Biology · doi:10.1038/ncb2038 · Cited by 201
Strategies targeting cellular senescence
Ovadya, Y., & Krizhanovsky, V. (2018) · Journal of Clinical Investigation · doi:10.1172/jci95149 · Cited by 200
Norval, M., Cullen, A. P., de Gruijl, F. R., Longstreth, J., Takizawa, Y., Lucas, R. M., Noonan, F. P., & van der Leun, J. C. (2007) · Photochemical & Photobiological Sciences · doi:10.1039/b700018a · Cited by 199
Fan, T., Jiang, S., Chung, N., Alikhan, A., Ni, C., Lee, C. R., & Hornyak, T. J. (2011) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-10-0511 · Cited by 199
Raabe, E. H., Lim, K. S., Kim, J. M., Meeker, A. K., Mao, X., Nikkhah, G., Maciaczyk, J., Kahlert, U. D., Jain, D., Bar, E. E., et al. (2011) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-10-3349 · Cited by 199
Targeting oncogenic Raf protein-serine/threonine kinases in human cancers
Roskoski, R. J. (2018) · Pharmacological Research · doi:10.1016/j.phrs.2018.08.013 · Cited by 199
Senescence as a therapeutic target in cancer and age-related diseases
McHugh, D., Durán, I., & Gil, J. (2025) · Nature Reviews Drug Discovery · doi:10.1038/s41573-024-01074-4 · Cited by 197
A comparative analysis of the cell biology of senescence and aging
Hwang, E. S., Yoon, G., & Kang, H. T. (2009) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-009-0034-2 · Cited by 198
Size Does Matter: Why Polyploid Tumor Cells are Critical Drug Targets in the War on Cancer
Coward, J. I. G., & Harding, A. S. (2014) · Frontiers in Oncology · doi:10.3389/fonc.2014.00123 · Cited by 197
Algorithmic assessment of cellular senescence in experimental and clinical specimens
Kohli, J., Wang, B., Brandenburg, S. M., Basisty, N., Evangelou, K., Varela-Eirin, M., Campisi, J., Schilling, B., Gorgoulis, V., & Demaria, M. (2021) · Nature Protocols · doi:10.1038/s41596-021-00505-5 · Cited by 196
Hocker, T. L. H., Singh, M. K., & Tsao, H. (2008) · Journal of Investigative Dermatology · doi:10.1038/jid.2008.226 · Cited by 196
Tumor suppressor activity of the ERK/MAPK pathway by promoting selective protein degradation
Deschênes-Simard, X., Gaumont-Leclerc, M.-F., Bourdeau, V., Lessard, F., Moiseeva, O., Forest, V., Igelmann, S., Mallette, F. A., Saba-El-Leil, M. K., Meloche, S., et al. (2013) · Genes & Development · doi:10.1101/gad.203984.112 · Cited by 194
Acquired and intrinsic BRAF inhibitor resistance in BRAF V600E mutant melanoma
Smalley, I., Paraiso, K. H. T., & Smalley, K. S. M. (2011) · Biochemical Pharmacology · doi:10.1016/j.bcp.2011.05.015 · Cited by 194
Cellular Senescence in Postmitotic Cells: Beyond Growth Arrest
Sapieha, P., & Mallette, F. A. (2018) · Trends in Cell Biology · doi:10.1016/j.tcb.2018.03.003 · Cited by 193
Therapeutic interventions for aging: the case of cellular senescence
Soto-Gamez, A., & Demaria, M. (2017) · Drug Discovery Today · doi:10.1016/j.drudis.2017.01.004 · Cited by 192
Analysis of the genome to personalize therapy for melanoma
Davies, M. A., & Samuels, Y. (2010) · Oncogene · doi:10.1038/onc.2010.323 · Cited by 190
Palmieri, G., Capone, M., Ascierto, M. L., Gentilcore, G., Stroncek, D. F., Casula, M., Sini, M. C., Palla, M., Mozzillo, N., & Ascierto, P. A. (2009) · Journal of Translational Medicine · doi:10.1186/1479-5876-7-86 · Cited by 190
Uncovering and Dissecting the Genotoxicity of Self-inactivating Lentiviral Vectors In Vivo
Cesana, D., Ranzani, M., Volpin, M., Bartholomae, C., Duros, C., Artus, A., Merella, S., Benedicenti, F., Sergi Sergi, L., Sanvito, F., et al. (2014) · Molecular Therapy · doi:10.1038/mt.2014.3 · Cited by 189
Liu, W. J., Kelly, J. W., Trivett, M. K., Murray, W. K., Dowling, J. P., Wolfe, R. S., Mason, G., Magee, J., Angel, C. M., Dobrovic, A., et al. (2006) · Journal of Investigative Dermatology · doi:10.1038/sj.jid.5700632 · Cited by 189
Liu, H., He, Z., von Rütte, T., Yousefi, S., Hunger, R. E., & Simon, H.-U. (2013) · Science Translational Medicine · doi:10.1126/scitranslmed.3005864 · Cited by 188
Assessing cell and organ senescence biomarkers
de Jesus, B. B., & Blasco, M. A. (2012) · Circulation Research · doi:10.1161/circresaha.111.247866 · Cited by 187
Cellular senescence and the tumour microenvironment
Takasugi, M., Yoshida, Y., & Ohtani, N. (2022) · Molecular Oncology · doi:10.1002/1878-0261.13268 · Cited by 190
Bennecke, 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
Majumder, P. K., Grisanzio, C., O’Connell, F., Barry, M., Brito, J. M., Xu, Q., Guney, I., Berger, R., Herman, P. K., Bikoff, R., et al. (2008) · Cancer Cell · doi:10.1016/j.ccr.2008.06.002 · Cited by 186
Detection 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
Tumor Stroma-Derived TGF-β Limits Myc-Driven Lymphomagenesis via Suv39h1-Dependent Senescence
Reimann, M., Lee, S., Loddenkemper, C., Dörr, J. R., Tabor, V., Aichele, P., Stein, H., Dörken, B., Jenuwein, T., & Schmitt, C. A. (2010) · Cancer Cell · doi:10.1016/j.ccr.2009.12.043 · Cited by 184
Sensi, M., Nicolini, G., Petti, C., Bersani, I., Lozupone, F., Molla, A., Vegetti, C., Nonaka, D., Mortarini, R., Parmiani, G., et al. (2006) · Oncogene · doi:10.1038/sj.onc.1209379 · Cited by 183
Stable Cellular Senescence Is Associated with Persistent DDR Activation
Fumagalli, M., Rossiello, F., Mondello, C., & d’Adda di Fagagna, F. (2014) · PLoS ONE · doi:10.1371/journal.pone.0110969 · Cited by 183
ATR signaling can drive cells into senescence in the absence of DNA breaks
Toledo, L. I., Murga, M., Gutierrez-Martinez, P., Soria, R., & Fernandez-Capetillo, O. (2008) · Genes & Development · doi:10.1101/gad.452308 · Cited by 183
BRAF as therapeutic target in melanoma
Wellbrock, C., & Hurlstone, A. F. L. (2010) · Biochemical Pharmacology · doi:10.1016/j.bcp.2010.03.019 · Cited by 183
Cancer and ageing: convergent and divergent mechanisms
Serrano, M., & Blasco, M. A. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2242 · Cited by 182
Senescence-Associated β-Galactosidase Detection in Pathology
Valieva, Y., Ivanova, E., Fayzullin, A., Kurkov, A., & Igrunkova, A. (2022) · Diagnostics · doi:10.3390/diagnostics12102309 · Cited by 182
Necessary and Sufficient Role for a Mitosis Skip in Senescence Induction
Johmura, Y., Shimada, M., Misaki, T., Naiki-Ito, A., Miyoshi, H., Motoyama, N., Ohtani, N., Hara, E., Nakamura, M., Morita, A., et al. (2014) · Molecular Cell · doi:10.1016/j.molcel.2014.05.003 · Cited by 182
Adams, P. D. (2007) · Gene · doi:10.1016/j.gene.2007.04.020 · Cited by 182
NRAS mutant melanoma: biological behavior and future strategies for therapeutic management
Fedorenko, I. V., Gibney, G. T., & Smalley, K. S. M. (2012) · Oncogene · doi:10.1038/onc.2012.453 · Cited by 180
Histone macroH2A isoforms predict the risk of lung cancer recurrence
Sporn, J. C., Kustatscher, G., Hothorn, T., Collado, M., Serrano, M., Muley, T., Schnabel, P. A., & Ladurner, A. G. (2009) · Oncogene · doi:10.1038/onc.2009.26 · Cited by 179
Spatial and Temporal Control of Senescence
Ito, Y., Hoare, M., & Narita, M. (2017) · Trends in Cell Biology · doi:10.1016/j.tcb.2017.07.004 · Cited by 178
SIRT1 and AMPK in regulating mammalian senescence: A critical review and a working model
Wang, Y., Liang, Y. Q., & Vanhoutte, P. M. (2010) · FEBS Letters · doi:10.1016/j.febslet.2010.11.047 · Cited by 178
Lyu, G., Guan, Y., Zhang, C., Zong, L., Sun, L., Huang, X., Huang, L., Zhang, L., Tian, X., Zhou, Z., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-04994-z · Cited by 178
Regulation of E2Fs and senescence by PML nuclear bodies
Vernier, M., Bourdeau, V., Gaumont-Leclerc, M.-F., Moiseeva, O., Bégin, V., Saad, F., Mes-Masson, A.-M., & Ferbeyre, G. (2011) · Genes & Development · doi:10.1101/gad.1975111 · Cited by 177
WNT5A Expression Increases during Melanoma Progression and Correlates with Outcome
Forno, P. D. D., Pringle, J. H., Hutchinson, P. J., Osborn, J., Huang, Q., Potter, L., Hancox, R. A., Fletcher, A., & Saldanha, G. S. (2008) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-07-5104 · Cited by 177
Ye, X., Zerlanko, B. J., Zhang, R., Somaiah, N., Lipinski, M., Salomoni, P., & Adams, P. D. (2007) · Molecular and Cellular Biology · doi:10.1128/mcb.01592-06 · Cited by 177
Melanocytic nevus-like hyperplasia and melanoma in transgenic BRAFV600E mice
Goel, V., Ibrahim, N., Jiang, G., Singhal, M., Fee, S., Flotte, T. J., Westmoreland, S. V., Haluska, F. S., Hinds, P. W., & Haluska, F. G. (2009) · Oncogene · doi:10.1038/onc.2009.95 · Cited by 176
The lncRNA MIR31HG regulates p16INK4A expression to modulate senescence
Montes, M., Nielsen, M. M., Maglieri, G., Skanderup, A. J., Højfeldt, J. W., Singh, S. A., Hansen, K. H., Helin, K., van de Werken, H. J. G., Pedersen, J. S., et al. (2015) · Nature Communications · doi:10.1038/ncomms7967 · Cited by 176
Rebecca, V. W., Sondak, V. K., & Smalley, K. S. M. (2012) · Melanoma Research · doi:10.1097/cmr.0b013e328351fa4d · Cited by 176
A Prospective Study of Telomere Length and the Risk of Skin Cancer
Han, J., Qureshi, A. A., Prescott, J., Guo, Q., Ye, L., Hunter, D. J., & Vivo, I. D. (2008) · Journal of Investigative Dermatology · doi:10.1038/jid.2008.238 · Cited by 175
Metabolic rewiring in melanoma
Ratnikov, B. I., Scott, D. A., Osterman, A. L., Smith, J. W., & Ronai, Z. A. (2016) · Oncogene · doi:10.1038/onc.2016.198 · Cited by 176
Lessard, F., Igelmann, S., Trahan, C., Huot, G., Saint-Germain, E., Mignacca, L., Del Toro, N., Lopes-Paciencia, S., Le Calvé, B., Montero, M., et al. (2018) · Nature Cell Biology · doi:10.1038/s41556-018-0127-y · Cited by 174
Senescence in chronic liver disease: Is the future in aging?
Aravinthan, A. D., & Alexander, G. J. M. (2016) · Journal of Hepatology · doi:10.1016/j.jhep.2016.05.030 · Cited by 174
Jacob, K., Khuong-Quang, D.-A., Jones, D., Witt, H., Lambert, S. R., Albrecht, S., Witt, O., Vézina, C., Shirinian, M., Faury, D., et al. (2011) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-11-0127 · Cited by 174
Tumor suppressor p16 INK4A is necessary for survival of cervical carcinoma cell lines
McLaughlin-Drubin, M. E., Park, D., & Münger, K. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1310432110 · Cited by 173
Hyperplastic and Serrated Polyps of the Colorectum
O’Brien, M. J. (2007) · Gastroenterology Clinics of North America · doi:10.1016/j.gtc.2007.08.007 · Cited by 173
Real-time in vivo imaging of p16Ink4a reveals cross talk with p53
Yamakoshi, K., Takahashi, A., Hirota, F., Nakayama, R., Ishimaru, N., Kubo, Y., Mann, D. J., Ohmura, M., Hirao, A., Saya, H., et al. (2009) · Journal of Cell Biology · doi:10.1083/jcb.200904105 · Cited by 172
STAT3 regulated ARF expression suppresses prostate cancer metastasis
Pěnčík, J., Schlederer, M., Gruber, W., Unger, C., Walker, S. M., Chalaris, A., Marié, I. J., Hassler, M. R., Javaheri, T., Aksoy, O., et al. (2015) · Nature Communications · doi:10.1038/ncomms8736 · Cited by 172
The Senescence-Associated Secretory Phenotype: Critical Effector in Skin Cancer and Aging
Ghosh, K., & Capell, B. C. (2016) · Journal of Investigative Dermatology · doi:10.1016/j.jid.2016.06.621 · Cited by 171
Dow, L. E., Elsum, I. A., King, C. L., Kinross, K. M., Richardson, H. E., & Humbert, P. O. (2008) · Oncogene · doi:10.1038/onc.2008.219 · Cited by 171
SIRT1 suppresses the senescence-associated secretory phenotype through epigenetic gene regulation
Hayakawa, T., Iwai, M., Aoki, S., Takimoto, K., Maruyama, M., Maruyama, W., & Motoyama, N. (2015) · PLOS ONE · doi:10.1371/journal.pone.0116480 · Cited by 170
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
Paul, R., Dorsey, J. F., & Fan, Y. (2021) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2021.107985 · Cited by 170
Le, O. N. L., Rodier, F., Fontaine, F., Coppe, J., Campisi, J., DeGregori, J., Laverdière, C., Kokta, V., Haddad, E., & Beauséjour, C. M. (2010) · Aging Cell · doi:10.1111/j.1474-9726.2010.00567.x · Cited by 168
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
