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Rb Regulates DNA Damage Response and Cellular Senescence through E2F-Dependent Suppression of N-Ras Isoprenylation
Open accessAbstract
Oncogene-induced cellular senescence is well documented, but little is known about how infinite cell proliferation induced by loss of tumor suppressor genes is antagonized by cellular functions. Rb heterozygous mice generate Rb-deficient C cell adenomas that progress to adenocarcinomas following biallelic loss of N-ras. Here, we demonstrate that pRb inactivation induces aberrant expression of farnesyl diphosphate synthase, many prenyltransferases, and their upstream regulators sterol regulatory element-binding proteins (SREBPs) in an E2F-dependent manner, leading to enhanced isoprenylation and activation of N-Ras. Consequently, elevated N-Ras activity induces DNA damage response and p130-dependent cellular senescence in Rb-deficient cells. Furthermore, Rb heterozygous mice additionally lacking any of Ink4a, Arf, or Suv39h1 generated C cell adenocarcinomas, suggesting that cellular senescence antagonizes Rb-deficient carcinogenesis.
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“The loss of tumour suppressors, such as PTEN 23 (BOX 2), RB 27 , neurofribromin 1 (NF1) 28 and inositol polyphosphate-4-phosphatase, type II (INPP4B) 29 , has also been associated with senescence in premalignant tumours.”
From Inside and out: the activities of senescence in cancer (2014) · cites this paper as [27]
Citations
Cites
Hanahan, D., & Weinberg, R. A. (2000) · Cell · doi:10.1016/s0092-8674(00)81683-9 · Cited by 29,219
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
Todaro, G. J., & Green, H. (1963) · The Journal of Cell Biology · doi:10.1083/jcb.17.2.299 · Cited by 2,747
ATM and related protein kinases: safeguarding genome integrity
Shiloh, Y. (2003) · Nature Reviews Cancer · doi:10.1038/nrc1011 · Cited by 2,577
Rb-mediated heterochromatin formation and silencing of E2F target genes during cellular senescence
Narita, M., Nuñez, S., Heard, E., Narita, M., Lin, A. W., Hearn, S. A., Spector, D. L., Hannon, G. J., & Lowe, S. W. (2003) · Cell · doi:10.1016/s0092-8674(03)00401-x · Cited by 2,278 · cited 2×
“We also detected senescence-associated heterochromatin foci (SAHF) (Narita et al., 2003) (Figure 3D) and high SA-b-gal activity (Figure 3F).”
BackgroundCrucial role of p53-dependent cellular senescence in suppression of Pten-deficient tumorigenesis
Chen, Z., Trotman, L. C., Shaffer, D., Lin, H.-K., Dotan, Z. A., Niki, M., Koutcher, J. A., Scher, H. I., Ludwig, T., Gerald, W., et al. (2005) · Nature · doi:10.1038/nature03918 · Cited by 1,993
Loss of the Suv39h Histone Methyltransferases Impairs Mammalian Heterochromatin and Genome Stability
Peters, A. H. F. M., O'Carroll, D., Scherthan, H., Mechtler, K., Sauer, S., Schöfer, C., Weipoltshammer, K., Pagani, M., Lachner, M., Kohlmaier, A., et al. (2001) · Cell · doi:10.1016/s0092-8674(01)00542-6 · Cited by 1,766
Effects of an Rb mutation in the mouse
Jacks, T., Fazeli, A., Schmitt, E. M., Bronson, R. T., Goodell, M. A., & Weinberg, R. A. (1992) · Nature · doi:10.1038/359295a0 · Cited by 1,755
Cellular senescence in cancer and aging.
Collado, M., Blasco, M. A., & Serrano, M. (2007) · Cell · doi:10.1016/j.cell.2007.07.003 · Cited by 1,708
Role of the INK4a Locus in Tumor Suppression and Cell Mortality
Serrano, M., Lee, H.-W., Chin, L., Cordon-Cardo, C., Beach, D., & DePinho, R. A. (1996) · Cell · doi:10.1016/s0092-8674(00)81079-x · Cited by 1,585
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Items 101–139 of 139
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Ruidas, B. (2024) · Mitochondrial Communications · doi:10.1016/j.mitoco.2024.07.001 · Cited by 6
RB1 loss induces quiescent state through downregulation of RAS signaling in mammary epithelial cells
Gong, L., Voon, D. C., Nakayama, J., Takahashi, C., & Kohno, S. (2024) · Cancer Science · doi:10.1111/cas.16122 · Cited by 4
Self-citationRB1 controls differentiation through positive regulation of phosphoglycerate mutases
Kohno, S., Okahashi, N., Wan, Y., Yu, H., Takegami, Y., Linn, P., Nagatani, N., Kitajima, S., Kawada, T., Matsuda, F., et al. (2025) · Cell Death and Disease · doi:10.1038/s41419-025-07850-3 · Cited by 4
Self-citationAging of Human Mesenchymal Stem Cells
Lin, H., Shen, H., & Tuan, R. S. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-811353-0.00071-3 · Cited by 3
Ras and pRb: The Relationship Gets Yet More Intimate
Peeper, D. S. (2009) · Cancer Cell · doi:10.1016/j.ccr.2009.03.007 · Cited by 3
Cancer RNome: Evolution and Sustenance
Arora, M., & Kaul, D. (2018) · Springer eBooks · doi:10.1007/978-981-13-1568-8_3 · Cited by 3
SARS-CoV-2 spike triggers TLR7-dependent endolysosome dysfunction and senescence in human astrocytes
Hasler, W. A., McKay, E., Datta, G., Johnson, S., Rezagholizadeh, N., & Chen, X. (2025) · Journal of Neuroinflammation · doi:10.1186/s12974-025-03586-1 · Cited by 2
Deprivation of EGFR signal causes senolysis in PDAC with CDK4/6 inhibition
Zhang, Y., Kohno, S., Gao, K., Hasan, M., Baba, T., Zhang, Z., Sankoda, N., Yu, H., Pan, J., Gotoh, N., et al. (2025) · Cell Death and Differentiation · doi:10.1038/s41418-025-01634-0 · Cited by 2
Self-citationPro-senescence Therapy for Cancer: Time for the Clinic
Kalathur, M., Mitri, D. D., & Alimonti, A. (2014) · Springer eBooks · doi:10.1007/978-94-017-9421-3_8 · Cited by 2
Xu, D., Li, S., Zhang, M., & Sun, Y. (2014) · Critical Reviews in Environmental Science and Technology · doi:10.1080/10643389.2013.852409 · Cited by 2
The Effects of Sterol-Related Signaling Pathways on Glioma
Eslahi, M., Dana, P. M., Sadoughi, F., Hallajzadeh, J., Asemi, Z., Sharifi, M., Mansournia, M. A., & Yousefi, B. (2021) · Nutrition and Cancer · doi:10.1080/01635581.2021.1957488 · Cited by 2
The Senescence Secretome and Its Impact on Tumor Suppression and Cancer
Kennedy, A. L., & Adams, P. D. (2010) · Springer eBooks · doi:10.1007/978-1-4419-1770-6_9 · Cited by 1
The RB Epigenetic Functions in Cancer Progression Control
Shamma, A. (2013) · Journal of Cancer Biology & Research · Cited by 1
Self-citationPleiotropic Functions of RB Protein in Tumor Suppression
Hayashi, N., & Takahashi, C. (2015) · Archives in Cancer Research · doi:10.21767/2254-6081.100022 · Cited by 1
Self-citationA causal role of ATM- and NEMO-dependent NF-κB activation in DNA damage-induced senescence and aging
Zhao, J. (2016) · D-Scholarship@Pitt (University of Pittsburgh) · Cited by 1
Exploiting Senescence for Cancer Treatment
Gadhikar, M. A., & Singh, P. K. (2016) · Molecular Biology · doi:10.4172/2168-9547.1000172 · Cited by 1
CHROMO domain readers: A rainbow of opportunities
Sun, X. S., Shrestha, P., & Mills, A. A. (2023) · Elsevier eBooks · doi:10.1016/b978-0-12-823376-4.00009-4 · Cited by 1
The Characteristics of Tumor Metabolism and Its Application Progress in Tumor Therapy
张, 城. (2024) · Advances in Clinical Medicine · doi:10.12677/acm.2024.1461863 · Cited by 1
Use of RNA Interference to Study DNA Repair
Fouquerel, E., Li, J., Braganza, A., Yu, Z., Brown, A. R., Wang, X., Schamus, S., Svilar, D., Fang, Q., & Sobol, R. W. (2014) · Methods in pharmacology and toxicology · doi:10.1007/978-1-4939-1068-7_24 · Cited by 1
McCarthy, N. J. (2009) · Nature reviews. Cancer · doi:10.1038/nrc2660 · Cited by 1
[Research advances on RB1 gene].
Liu, S.-H., Wang, S.-Z., Zhang, H., & Li, H. (2010) · PubMed · Cited by 1
The retinoblastoma protein mediates metabolic reprogramming in lung cancer.
Conroy, L. R. (2020) · ThinkIR: The University of Louisville's Institutional Repository (University of Louisville) · doi:10.18297/etd/3405 · Cited by 1
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Cadar, A. E. (2014) · doi:10.71781/31878
Nidadavolu, L. S. (2013) · D-Scholarship@Pitt (University of Pittsburgh)
Generation of Mouse Thyroid Calcitonin-producing Cell Tumors from Primary Mouse Tumors
Kitajima, S., Li, F., & Takahashi, C. (2015) · BIO-PROTOCOL · doi:10.21769/bioprotoc.1681
Self-citationTHE ACTIVATION AND CONSEQUENCES OF THE ATM MEDIATED DNA DAMAGE RESPONSE IN HPV INFECTED CELLS
Johnson, B. A. (2019) · Carolina Digital Repository (University of North Carolina at Chapel Hill) · doi:10.17615/wbp3-aa71
Synthetic Inhibitors of CDK4/6 Activities and Tumor Suppression: A Preface to the Special Issue
Takahashi, C., & Kato, J. (2021) · Onco · doi:10.3390/onco1010001
Self-citationJiang, A., Mao, L., Duan, S., Zhang, Y., Liu, X., Cui, W., Sang, Y., & Huang, G. (2020) · doi:10.21203/rs.3.rs-23760/v1
Duttaroy, A. K. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-822405-2.00013-x
ASPP2, a New Regulator of the Mevalonate Pathway in Cancer
Liang, B., Xie, Y., Zhang, L., & Zhao, J. (2022) · Journal of Cancer Treatment and Diagnosis · doi:10.29245/2578-2967/2022/1.1198
Alsiary, R., Katouah, H. A., Al-Amodi, H. S. A. B., & Al-Toub, M. (2023) · BENTHAM SCIENCE PUBLISHERS eBooks · doi:10.2174/9789815080384123010007
Jeong, D.-W., Lee, S., & Chun, Y.-S. (2021) · Figshare · doi:10.6084/m9.figshare.17010237
Multifacet Roles of Cellular Senescence in Cancer: Mechanisms and Therapeutic Implications
Mao, H., Liu, W., Su, Y., Ma, Y., Zhao, X., & Lu, Y. (2026) · MedComm – Oncology · doi:10.1002/mog2.70060 · Cited by 1
Sénescence cellulaire et nouvelles approches thérapeutiques de l'hypertension artérielle pulmonaire
Mouraret, N. (2013) · theses.fr (ABES) · doi:10.70675/b2ae892dzafc0z4b55z9d55zb8908a6a07c7
Generation of antisense RNAs at convergent gene loci in cells undergoing senescence
Deb, M. K. (2016) · theses.fr (ABES) · doi:10.70675/739ebf07zf620z4e1fzb0d4z02066589491f
Glioblastoma resistance to temozolomide : implication of α5β1 integrin and p53 signalling pathways
Sani, S. (2020) · theses.fr (ABES) · doi:10.70675/9566c585z0508z455bz9064z6bb61435b210
López, Á., & Jesús, M. (2015) · Dipòsit Digital de la Universitat de Barcelona (Universitat de Barcelona)
Metadata
- Authors
- Shamma, A., Takegami, Y., Miki, T., Kitajima, S., Noda, M., Obara, T., Okamoto, T., & Takahashi, C.
- Affiliations
- Kyoto University (JP)
- Tokyo Women's Medical University (JP)
- Corresponding author
- Takahashi, Chiaki
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2009-04
- Volume
- 15
- Issue
- 4
- Pages
- 255-269
- ISSN
- 1535-6108 (ISSN-L)
- OpenAlex
- W2122846804
- Cited by
- 140
- References
- 63
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 8 · 2023: 5 · 2022: 6 · 2021: 14 · 2020: 10 · 2019: 12 · 2018: 5 · 2017: 7 · 2016: 10 · 2015: 11 · 2014: 11 · 2013: 9 · 2012: 7
- FWCI
- 5.96
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cancer Cell (publishedVersion)
- PubMed (publishedVersion)
- Institutional Repositories DataBase (IRDB) (submittedVersion)
- Institutional Repositories DataBase (IRDB) (submittedVersion, cc-by-nc-nd)
- Kanazawa University Repository for Academic Resources (DSpace) (Kanazawa University) (submittedVersion, cc-by-nc-nd)
- Kyoto University Research Information Repository (Kyoto University) (submittedVersion)
- Funders
- Princess Takamatsu Cancer Research Fund
- Takeda Science Foundation
- Ministry of Education, Culture, Sports, Science and Technology
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Keywords
- retinoblastoma protein, oncogene-induced senescence, NRAS, isoprenylation, DNA damage response, E2F transcription factors, farnesyl diphosphate synthase, prenyltransferase, SREBP, p130, INK4A, ARF, SUV39H1, tumor suppressor inactivation, carcinogenesis
- MeSH terms
- Adenocarcinoma, Adenoma, Animals, Cell Membrane, DNA Damage, DNA Repair, Humans, Immunoenzyme Techniques, Genes, ras, Thyroid Neoplasms, Retinoblastoma Protein, Cellular Senescence, Protein Prenylation, Mice, Knockout, Cyclin-Dependent Kinase Inhibitor p16, Brain Stem Neoplasms, Protein Transport, Chromatin Immunoprecipitation, E2F Transcription Factors, Mice, Prenylation
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