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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.
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“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.
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“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]
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“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]
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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
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)
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Items 801–900 of 1,009
Krejčí, P. (2013) · Mutation Research/Reviews in Mutation Research · doi:10.1016/j.mrrev.2013.11.001 · Cited by 51
Oncogene-induced senescence: An essential role for Runx
Terry, A., Cameron, E. R., Neil, J. C., & Kilbey, A. (2008) · Cell Cycle · doi:10.4161/cc.6368 · Cited by 51
Kihara, A., Yoshida, H., Watanabe, R., Takahashi, K., Kato, T., Ino, Y., Kitagawa, M., & Hiraoka, N. (2017) · The American Journal of Surgical Pathology · doi:10.1097/pas.0000000000000856 · Cited by 51
Aberrant expression of p16INK4a in human cancers – a new biomarker?
Inoue, K., & Fry, E. A. (2018) · Cancer Reports and Reviews · doi:10.15761/crr.1000145 · Cited by 51
Drug-induced senescence bystander proliferation in prostate cancer cells in vitro and in vivo
Ewald, J. A., Desotelle, J. A., Almassi, N., & Jarrard, D. F. (2008) · British Journal of Cancer · doi:10.1038/sj.bjc.6604288 · Cited by 51
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Cavalli, G., Biavasco, R., Borgiani, B., & Dagna, L. (2014) · Frontiers in Immunology · doi:10.3389/fimmu.2014.00281 · Cited by 50
Cell senescence as both a dynamic and a static phenotype
Young, A. R. J., Narita, M., & Narita, M. (2013) · Methods in Molecular Biology · doi:10.1007/978-1-62703-239-1_1 · Cited by 50
Brauer, E., Lange, T., Keller, D., Görlitz, S., Cho, S., Keye, J., Gossen, M., Petersen, A., & Kornak, U. (2022) · Aging Cell · doi:10.1111/acel.13744 · Cited by 50
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O’Sullivan, E. A., Wallis, R., Mossa, F., & Bishop, C. L. (2024) · npj Aging · doi:10.1038/s41514-024-00168-y · Cited by 50
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Chesnokova, V., & Melmed, S. K. (2010) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2010.02.012 · Cited by 50
Nijwening, J. H., Geutjes, E.-J., Bernards, R., & Beijersbergen, R. L. (2011) · PLoS ONE · doi:10.1371/journal.pone.0025235 · Cited by 50
Hansson, J. (2010) · Advances in experimental medicine and biology · doi:10.1007/978-1-4419-6448-9_13 · Cited by 50
RUNX2 is overexpressed in melanoma cells and mediates their migration and invasion
Boregowda, R. K., Olabisi, O. O., Abushahba, W., Jeong, B., Haenssen, K. K., Chen, W., Chekmareva, M. A., Lasfar, A., Foran, D. J., Goydos, J. S., et al. (2014) · Cancer Letters · doi:10.1016/j.canlet.2014.03.011 · Cited by 50
BRAF mutations in pediatric metanephric tumors
Chami, R., Yin, M., Marrano, P. M., Teerapakpinyo, C., Shuangshoti, S., & Thorner, P. S. (2015) · Human Pathology · doi:10.1016/j.humpath.2015.03.019 · Cited by 50
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Shepherd, C., Puzanov, I. J., & Sosman, J. A. (2010) · Current Oncology Reports · doi:10.1007/s11912-010-0095-2 · Cited by 50
Melanomagenesis: Overcoming the barrier of melanocyte senescence
Ha, L., Merlino, G. T., & Sviderskaya, E. V. (2008) · Cell Cycle · doi:10.4161/cc.7.13.6230 · Cited by 50
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Li, Q., Zhang, Y., Fu, J., Han, L., Xue, L., Lv, C., Wang, P., Li, G., & Tong, T. (2013) · The EMBO Journal · doi:10.1038/emboj.2013.35 · Cited by 50
Schultz, J., Ibrahim, S. M., Vera, J., & Kunz, M. (2009) · Molecular Cancer · doi:10.1186/1476-4598-8-53 · Cited by 50
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DeLuca, A. M., Srinivas, A., & Alani, R. M. (2008) · Expert Reviews in Molecular Medicine · doi:10.1017/s1462399408000604 · Cited by 50
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Haedo, M. R., Gerez, J., Fuertes, M., Giacomini, D., Páez-Pereda, M., Labeur, M. S., Renner, U., Stalla, G. K., & ARZT, E. S. (2009) · Hormone Research in Paediatrics · doi:10.1159/000245928 · Cited by 50
Zheng, H., Seit‐Nebi, A. S., Han, X., Aslanian, A., Tat, J., Liao, R., Yates, J. R., & Sun, P. (2013) · Molecular Cell · doi:10.1016/j.molcel.2013.04.013 · Cited by 50
miR-125b induces cellular senescence in malignant melanoma
Nyholm, A. M., Lerche, C. M., Manfé, V., Biskup, E., Johansen, P., Morling, N., Thomsen, B. M., Glud, M., & Gniadecki, R. (2014) · BMC Dermatology · doi:10.1186/1471-5945-14-8 · Cited by 50
Gene expression signature associated with BRAF mutations in human primary cutaneous melanomas
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Wajapeyee, N., Kapoor, V., Mahalingam, M., & Green, M. R. (2009) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-09-0470 · Cited by 50
Knösel, T., Altendorf-Hofmann, A., Lindner, L. H., Issels, R. D., Hermeking, H., Schuebbe, G., Gibis, S., Siemens, H., Kampmann, E., & Kirchner, T. (2014) · Journal of Clinical Pathology · doi:10.1136/jclinpath-2013-202106 · Cited by 50
An update on the implications of cyclin D1 in melanomas
González‐Ruiz, L., González‐Moles, M. Á., González‐Ruiz, I., Ruiz‐Ávila, I., Ayén, Á., & Ramos‐García, P. (2020) · Pigment Cell & Melanoma Research · doi:10.1111/pcmr.12874 · Cited by 49
After Nf1 loss in Schwann cells, inflammation drives neurofibroma formation
Fletcher, J. S., Pundavela, J., & Ratner, N. (2019) · Neuro-Oncology Advances · doi:10.1093/noajnl/vdz045 · Cited by 49
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Godwin, L. S., Castle, J. T., Kohli, J. S., Goff, P. S., Cairney, C. J., Keith, W. N., Sviderskaya, E. V., & Bennett, D. C. (2014) · Current Protocols in Cell Biology · doi:10.1002/0471143030.cb0108s63 · Cited by 49
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Despars, G., Carbonneau, C. L., Bardeau, P., Coutu, D. L., & Beausejour, C. M. (2013) · PLoS ONE · doi:10.1371/journal.pone.0073206 · Cited by 49
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Nakano, M., Nakashima, A., Nagano, T., Ishikawa, S., Kikkawa, U., & Kamada, S. (2013) · PLoS ONE · doi:10.1371/journal.pone.0080411 · Cited by 49
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Muñoz-Galván, S., Lucena-Cacace, A., Pérez, M., Otero-Albiol, D., Gómez-Cambronero, J., & Carnero, A. (2018) · Oncogene · doi:10.1038/s41388-018-0527-2 · Cited by 49
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Miyasaka, Y., Nagai, E., Yamaguchi, H., Fujii, K., Inoue, T., Ohuchida, K., Yamada, T., Mizumoto, K., Tanaka, M., & Tsuneyoshi, M. (2007) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-07-0032 · Cited by 48
Axanova, L. S., Chen, Y. Q., McCoy, T. P., Sui, G., & Cramer, S. D. (2010) · The Prostate · doi:10.1002/pros.21201 · Cited by 48
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Bhatia, B., Multani, A. S., Patrawala, L., Chen, X., Calhoun‐Davis, T., Zhou, J., Schroeder, L., Schneider‐Broussard, R., Shen, J., Pathak, S., et al. (2008) · International Journal of Cancer · doi:10.1002/ijc.23222 · Cited by 47
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Pacheco, I., Buzea, C., & Tron, V. A. (2011) · Expert Reviews in Molecular Medicine · doi:10.1017/s146239941100202x · Cited by 47
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Park, J. (2014) · Frontiers in Biology · doi:10.1007/s11515-014-1299-x · Cited by 47
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Radspieler, M., Schindeldecker, M., Stenzel, P., Foersch, S., Tagscherer, K. E., Herpel, E., Hohenfellner, M., Hatiboglu, G., Roth, W., & Macher‐Goeppinger, S. (2019) · Oncology Letters · doi:10.3892/ol.2019.10593 · Cited by 47
mTOR pathway activation in cutaneous melanoma is associated with poorer prognosis characteristics
Pópulo, H., Soares, P., Faustino, A., Rocha, A. S., Silva, P., Azevedo, F., & Lopes, J. M. (2010) · Pigment Cell & Melanoma Research · doi:10.1111/j.1755-148x.2010.00796.x · Cited by 47
Senescence and apoptosis in carcinogenesis of cervical squamous carcinoma
Feng, W., Xiao, J., Zhang, Z., Rosen, D. G., Brown, R. E., Liu, J., & Duan, X. (2007) · Modern Pathology · doi:10.1038/modpathol.3800927 · Cited by 47
Gibney, G. T., & Smalley, K. S. M. (2013) · Cancer Discovery · doi:10.1158/2159-8290.cd-13-0017 · Cited by 47
A guide to ERK dynamics, part 2: downstream decoding
Ram, A. R., Murphy, D. A., DeCuzzi, N. L., Patankar, M., Hu, J. J., Pargett, M., & Albeck, J. G. (2023) · Biochemical Journal · doi:10.1042/bcj20230277 · Cited by 46
Subcellular structure, heterogeneity, and plasticity of senescent cells
Bitencourt, T. C., Vargas, J. E., Silva, A. O., Fraga, L. R., & Filippi‐Chiela, E. C. (2024) · Aging Cell · doi:10.1111/acel.14154 · Cited by 46
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Bajaj, S., Dusza, S. W., Marchetti, M. A., Wu, X., Fonseca, M., Köse, K., Brito, J., Carrera, C., de Silva, V. P. M., Malvehy, J., et al. (2015) · JAMA Dermatology · doi:10.1001/jamadermatol.2015.2231 · Cited by 46
PP2A-B56α controls oncogene-induced senescence in normal and tumor human melanocytic cells
Mannava, S., Omilian, A. R., Wawrzyniak, J. A., Fink, E. E., Zhuang, D., Miecznikowski, J. C., Marshall, J. R., Soengas, M. S., Sears, R. C., Morrison, C., et al. (2011) · Oncogene · doi:10.1038/onc.2011.339 · Cited by 46
Self-citationTihan, T., Erşen, A., Qaddoumi, I. A., Sughayer, M. A., Tolunay, Ş., Al-Hussaini, M. A., Phillips, J. J., Gupta, N. M., Goldhoff, P., & Baneerjee, A. (2011) · The American Journal of Surgical Pathology · doi:10.1097/pas.0b013e3182329480 · Cited by 46
Litwiniec, A., Grzanka, A., Helmin–Basa, A., Gackowska, L., & Grzanka, D. (2009) · Journal of Cancer Research and Clinical Oncology · doi:10.1007/s00432-009-0711-4 · Cited by 46
Venesio, T., Chiorino, G., Balsamo, A., Zaccagna, A., Petti, C., Scatolini, M., Pisacane, A. M., Sarotto, I., Picciotto, F., & Risio, M. (2008) · Modern Pathology · doi:10.1038/modpathol.2008.41 · Cited by 46
Bennani-Lahlou, M., Mateus, C., Escudier, B. J., Massard, C., Soria, J., Spatz, A., & Robert, C. (2008) · Annales de Dermatologie et de Vénéréologie · doi:10.1016/j.annder.2008.04.016 · Cited by 46
KRAS mutation testing in clinical practice
Perincheri, S., & Hui, P. (2014) · Expert Review of Molecular Diagnostics · doi:10.1586/14737159.2015.986102 · Cited by 46
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Caliò, A., Zamò, A., Ponzoni, M., Zanolin, M. E., Ferreri, A. J. M., Pedron, S., Montagna, L., Parolini, C., Fraifeld, V. E., Wolfson, M., et al. (2015) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-15-0508 · Cited by 46
Chilosi, M., Facchetti, F., Caliò, A., Zamò, A., Brunelli, M., Martignoni, G., Rossi, A., Montagna, L., Piccoli, P., Dubini, A., et al. (2014) · Leukemia & lymphoma/Leukemia and lymphoma · doi:10.3109/10428194.2014.887713 · Cited by 46
Extracellular acidosis triggers a senescence‐like phenotype in human melanoma cells
Böhme, I., & Bosserhoff, A. (2019) · Pigment Cell & Melanoma Research · doi:10.1111/pcmr.12811 · Cited by 46
Osanai, M., Murata, M., Nishikiori, N., Chiba, H., Kojima, T., & Sawada, N. (2007) · Cancer Science · doi:10.1111/j.1349-7006.2007.00494.x · Cited by 46
Skp2 Regulates G2/M Progression in a p53-dependent Manner
Hu, R., & Aplin, A. E. (2008) · Molecular Biology of the Cell · doi:10.1091/mbc.e07-11-1137 · Cited by 46
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Kohli, J. S., Chen, G., Fitsiou, E., Doepner, M., Brandenburg, S. M., Faller, W. J., Ridky, T. W., & Demaria, M. (2022) · Nature Communications · doi:10.1038/s41467-022-35657-9 · Cited by 45
The Complex Interplay between Nevi and Melanoma: Risk Factors and Precursors
Shreberk‐Hassidim, R., Ostrowski, S. M., & Fisher, D. E. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24043541 · Cited by 45
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Vergel, M., Marín, J., Estévez, P., & Carnero, A. (2010) · Journal of Aging Research · doi:10.4061/2011/725365 · Cited by 45
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Ruhland, M. K., & Alspach, E. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.754069 · Cited by 45
Oikonomou, E., Makrodouli, E., Evagelidou, M., Joyce, T., Probert, L., & Pintzas, A. (2009) · Neoplasia · doi:10.1593/neo.09514 · Cited by 45
Riemer, P., Sreekumar, A., Reinke, S., Rad, R., Schäfer, R., Sers, C., Bläker, H., Herrmann, B. G., & Morkel, M. (2014) · Oncogene · doi:10.1038/onc.2014.247 · Cited by 45
Neurofibromin as a regulator of melanocyte development and differentiation
Diwakar, G., Zhang, D., Jiang, S., & Hornyak, T. J. (2007) · Journal of Cell Science · doi:10.1242/jcs.013912 · Cited by 45
Altered senescence, apoptosis, and DNA damage response in a mutant p53 model of accelerated aging
Hinkal, G. W., Gatza, C. E., Parikh, N., & Donehower, L. A. (2009) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2009.01.001 · Cited by 45
Large cell change of hepatocytes in chronic viral hepatitis represents a senescent-related lesion
Ikeda, H., Sasaki, M., Sato, Y., Harada, K., Zen, Y., Mitsui, T., & Nakanuma, Y. (2009) · Human Pathology · doi:10.1016/j.humpath.2009.06.009 · Cited by 44
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
Normal development is an integral part of tumorigenesis in T cell-specific PTEN-deficient mice
Xue, L., Nolla, H. A., Suzuki, A., Mak, T. W., & Winoto, A. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0712059105 · Cited by 44
Kuo, M.-L., Sy, A. J., Xue, L., Chi, M., Lee, M. T. C., Yen, T., Chiang, M.-I., Chang, L., Chu, P. G., & Yen, Y. (2012) · Scientific Reports · doi:10.1038/srep00822 · Cited by 44
The integration of signaling by multiprotein complexes containing Raf kinases
Kyriakis, J. M. (2006) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2006.11.003 · Cited by 44
PTEN deletion in luminal cells of mature prostate induces replication stress and senescence in vivo
Parisotto, M., Grelet, E., El Bizri, R., Dai, Y., Terzic, J., Eckert, D., Gargowitsch, L., Bornert, J.-M., & Metzger, D. (2018) · Journal of Experimental Medicine · doi:10.1084/jem.20171207 · Cited by 43
Oncogene‐induced cellular senescence elicits an anti‐ Warburg effect
Li, M., Durbin, K. R., Sweet, S. M. M., Tipton, J. D., Zheng, Y., & Kelleher, N. L. (2013) · PROTEOMICS · doi:10.1002/pmic.201200298 · Cited by 43
Deregulated transcription factors in the emerging cancer hallmarks
Hasan, A., Khan, N. A., Shahab Uddin, M. S., Khan, A. Q., & Steinhoff, M. S. (2023) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2023.12.001 · Cited by 45
Lowe, R., Overhoff, M. G., Ramagopalan, S. V., Garbe, J. C., Koh, J., Stampfer, M. R., Beach, D., Rakyan, V. K., & Bishop, C. L. (2015) · Genome biology · doi:10.1186/s13059-015-0748-4 · Cited by 43
Lee, Y. H., Oh, B.-K., Yoo, J. E., Yoon, S.-M., Choi, J., Kim, K. S., & Park, Y. N. (2009) · Modern Pathology · doi:10.1038/modpathol.2009.76 · Cited by 43
Role of 2-5A-dependent RNase-L in senescence and longevity
Andersen, J. B., Li, X. L., Judge, C. S., Zhou, A., Jha, B. K., Shelby, S., Zhou, L., Silverman, R. H., & Hassel, B. A. (2006) · Oncogene · doi:10.1038/sj.onc.1210111 · Cited by 43
Lee, T., Paola, D. D., Malina, A., Mills, J. R., Kreps, A., Große, F., Tang, H., Zannis‐Hadjopoulos, M., Larsson, O. S., & Pelletier, J. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.568535 · Cited by 43
Niu, Y., Li, S., Pan, D., Liu, H., & Yao, X. (2016) · Physical Chemistry Chemical Physics · doi:10.1039/c5cp06257h · Cited by 43
The new paradigm of systemic therapies for metastatic melanoma
Volpe, V. O., Klufas, D. M., Hegde, U. P., & Grant-Kels, J. M. (2017) · Journal of the American Academy of Dermatology · doi:10.1016/j.jaad.2017.04.1126 · Cited by 43
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
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