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Non-Cell-Autonomous Tumor Suppression by p53
Open accessAbstract
The p53 tumor suppressor can restrict malignant transformation by triggering cell-autonomous programs of cell-cycle arrest or apoptosis. p53 also promotes cellular senescence, a tumor-suppressive program that involves stable cell-cycle arrest and secretion of factors that modify the tissue microenvironment. In the presence of chronic liver damage, we show that ablation of a p53-dependent senescence program in hepatic stellate cells increases liver fibrosis and cirrhosis associated with reduced survival and enhances the transformation of adjacent epithelial cells into hepatocellular carcinoma. p53-expressing senescent stellate cells release factors that skew macrophage polarization toward a tumor-inhibiting M1-state capable of attacking senescent cells in culture, whereas proliferating p53-deficient stellate cells secrete factors that stimulate polarization of macrophages into a tumor-promoting M2-state and enhance the proliferation of premalignant cells. Hence, p53 can act non-cell autonomously to suppress tumorigenesis by promoting an antitumor microenvironment, in part, through secreted factors that modulate macrophage function.
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“This response is mediated by SASP components and by the direct interaction between immune cells and senescent cells153,156–158.”
From Cellular senescence in ageing: from mechanisms to therapeutic opportunities (2021) · cites this paper as [153]
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
“activated HSCs become senescent, exhibiting a typical SASP, including the expression of extracellular matrix degrading enzymes and proinflammatory cytokines.”
From Inside and out: the activities of senescence in cancer (2014) · cites this paper as [94]
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
“and can recruit immune cells to contribute to cancer cell removal, reinforcing the tumor suppressive role of senescent tumor cells [263,266].”
From Mechanisms and Regulation of Cellular Senescence (2021) · cites this paper as [266]
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
“Senescent fibroblasts contribute to wound healing (Demaria et al. 2014), and the SASP of senescent hepatic stellate cells (HSCs) participates in fibrotic scar degradation and restores tissue homeostasis in liver fibrosis (Lujambio et al. 2013).”
From Senescence and the SASP: many therapeutic avenues (2020) · cites this paper as Lujambio et al. 2013
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In the citing paper
“This senescence-associated phenotype identified with secretion of pro-tumorigenic cytokines and chemokines can be restrained or qualitatively modified by p53 in several cell types in mouse [39, 41].”
From Ligand dependent restoration of human TLR3 signaling and death in p53 mutant cells (2016) · cites this paper as [41]
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“Senescent cells are indeed subjected to immunosurveillance by multiple components of innate and adaptive immunity, including NK cells, T cells and macrophages145,151,153–156.”
From Cellular senescence in ageing: from mechanisms to therapeutic opportunities (2021) · cites this paper as [153]
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In the citing paper
“Moreover, in a fibrosis-associated liver cancer model, the SASP can contribute to an anti-tumor microenvironment by skewing macrophage polarization to a tumor-inhibiting M1 state (Lujambio et al. 2013).”
From Senescence and the SASP: many therapeutic avenues (2020) · cites this paper as Lujambio et al. 2013
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“p53 cooperates with the NF- κB pathway to regulate SASP factors that can activate macrophages to form a tumour- suppressive microenvironment 147,148 .”
From Senescence and cancer — role and therapeutic opportunities (2022) · cites this paper as [148]
In the citing paper
“these secreted factors can stimulate the immune system to both suppress tumorigenesis and promote optimal repair of damaged tissues when senescent cells are removed after their beneficial actions (15–17).”
From The DNA damage response induces inflammation and senescence by inhibiting autophagy of GATA4. (2015) · cites this paper as [16]
In the citing paper
“Upon Dox withdrawal, senescence is induced by re-expression of p53 and mHSCs showed an increase in a number of markers of senescence (Figure S6A), concomitant with the accumulation of Itgb3”
From Integrin Beta 3 Regulates Cellular Senescence by Activating the TGF-β Pathway (2017) · cites this paper as Lujambio et al., 2013
In the citing paper
“The SASP also attracts innate immune cells that in turn eliminate the senescent HSCs and facilitate the resolution of fibrosis 94,120”
From Inside and out: the activities of senescence in cancer (2014) · cites this paper as [94]
In the citing paper
“Conversely, cells that could not become senescent due to p53 deletion were not targeted by macrophages [266].”
From Mechanisms and Regulation of Cellular Senescence (2021) · cites this paper as [266]
In the citing paper
“In mouse models, inactivating the senescence machinery results in the acceleration of tumor development, while restoration of senescence in growing tumors causes their regression consistent with the role of senescence in suppressing cancer [266,358].”
From Mechanisms and Regulation of Cellular Senescence (2021) · cites this paper as [266]
In the citing paper
“In mouse models, inactivating the senescence machinery results in the acceleration of tumor development, while restoration of senescence in growing tumors causes their regression consistent with the role of senescence in suppressing cancer [266,358].”
From Mechanisms and Regulation of Cellular Senescence (2021) · cites this paper as [266]
In the citing paper
“Additional immunostimulatory effects linked to pharmacological p53 reactivation in cancer cells include (but are not limited to) (1) downregulation of immunomodulatory cytokines linked to tumor progression, such as IL6 (Sahin et al., 2020); (2) upregulation of NKALs (Textor et al., 2011); and (3) establishment of cellular senescence linked to an immunostimulatory SASP that favors the recruitment”
From Immunomodulation by targeted anticancer agents (2021) · cites this paper as Lujambio et al., 2013
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Citations
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Self-citationBRD4 Connects Enhancer Remodeling to Senescence Immune Surveillance
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InfluentialSelf-citationSUMO and the robustness of cancer
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BackgroundQuantitative identification of senescent cells in aging and disease
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Mechanisms and Regulation of Cellular Senescence
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“Additionally, the secretome of directly affected tumor cells or adjacent senescent stromal fibroblasts can induce paracrine senescence of nearby tumor cells [270] and can recruit immune cells to contribute to cancer cell removal, reinforcing the tumor suppressive role of senescent tumor cells [263,266].”
BackgroundImmunological impact of cell death signaling driven by radiation on the tumor microenvironment
Rodriguez-Ruiz, M. E., Vitale, I., Harrington, K. J., Melero, I., & Galluzzi, L. (2020) · Nature Immunology · doi:10.1038/s41590-019-0561-4 · Cited by 385
Recurrent turnover of senescent cells during regeneration of a complex structure
Yun, M. H., Davaapil, H., & Brockes, J. P. (2015) · eLife · doi:10.7554/elife.05505 · Cited by 385
“…to be characteristic of regeneration, as no significant induction of senescence takes place during normal limb development (Figure 2E, Figure 2—figure supplement 2), in contrast to previous findings in amniotic limb development (Banito and Lowe, 2013; Munoz-Espin et al., 2013; Storer et al., 2013).”
ResultLong noncoding RNAs: Novel insights into hepatocelluar carcinoma
He, Y., Meng, X., Huang, C., Wu, B., Zhang, L., Lv, X., & Li, J. (2013) · Cancer Letters · doi:10.1016/j.canlet.2013.10.021 · Cited by 385
“As the p53 gene is an important tumor suppressor gene [40–42].”
BackgroundMacrophage Plasticity and Polarization in Liver Homeostasis and Pathology
Sica, A., Invernizzi, P., & Mantovani, A. (2014) · Hepatology · doi:10.1002/hep.26754 · Cited by 422
“By releasing factors that stimulate M2 macrophage polarization, p53-deficient stellate cells create a tumorpromoting environment.(56) Phagocytosis of dying necrotic cells and debris triggers production of TGF-b by KCs and recruited Fig.”
Aydin, M. M., & Akçalı, K. C. (2018) · The Turkish Journal of Gastroenterology · doi:10.5152/tjg.2018.17330 · Cited by 397
p16Ink4a-induced senescence of pancreatic beta cells enhances insulin secretion
Helman, A., Klochendler, A., Azazmeh, N., Gabai, Y., Horwitz, E., Anzi, S., Swisa, A., Condiotti, R., Granit, R. Z., Nevo, Y., et al. (2016) · Nature Medicine · doi:10.1038/nm.4054 · Cited by 351
Takahashi, A., Loo, T. M., Okada, R., Kamachi, F., Watanabe, Y., Wakita, M., Watanabe, S., Kawamoto, S., Miyata, K., Barber, G. N., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-03555-8 · Cited by 350
Opposing roles of hepatic stellate cell subpopulations in hepatocarcinogenesis
Filliol, A., Saito, Y., Nair, A., Dapito, D. H., Yu, L.-X., Ravichandra, A., Bhattacharjee, S., Affo, S., Fujiwara, N., Su, H., et al. (2022) · Nature · doi:10.1038/s41586-022-05289-6 · Cited by 349
Senescent cells and osteoarthritis: a painful connection
Jeon, O. H., David, N. E., Campisi, J., & Elisseeff, J. H. (2018) · Journal of Clinical Investigation · doi:10.1172/jci95147 · Cited by 359
“Senescent stellate cells secrete factors that favor macrophage polarization toward a proinflammatory M1 state, which also promotes SnC clearance (111).”
The Reprogramming of Tumor Stroma by HSF1 Is a Potent Enabler of Malignancy
Scherz-Shouval, R., Santagata, S., Mendillo, M. L., Sholl, L. M., Ben-Aharon, I., Beck, A. H., Dias-Santagata, D., Koeva, M., Stemmer, S. M., Whitesell, L., et al. (2014) · Cell · doi:10.1016/j.cell.2014.05.045 · Cited by 386
“In mouse models, tumor suppressors such as p53 and PTEN can act in the stroma to limit tumor growth (Lujambio et al., 2013; Moskovits et al., 2006; Trimboli et al., 2009).”
Therapy-Induced Senescence: Opportunities to Improve Anticancer Therapy
Prasanna, P. G. S., Citrin, D. E., Hildesheim, J., Ahmed, M. M., Venkatachalam, S., Riscuta, G., Xi, D., Zheng, G., van Deursen, J., Goronzy, J. J., et al. (2021) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djab064 · Cited by 359
“Similarly, activation of p53 in hepatic stellate cells due to senescence induced by CCl4 and the carcinogen diethyl-nitrosamine in mice reduced fibrosis and cirrhosis, besides inhibiting liver epithelial tumorigenesis because of immune clearance of SnCs (60).”
BackgroundSelf-citationRole of immune cells in the removal of deleterious senescent cells
Kale, A., Sharma, A., Stolzing, A., Desprez, P.-Y., & Campisi, J. (2020) · Immunity & Ageing · doi:10.1186/s12979-020-00187-9 · Cited by 351
“factors, which shift macrophages to the M2 state [59].”
BackgroundCellular senescence in renal ageing and disease
Sturmlechner, I., Durik, M., Sieben, C. J., Baker, D. J., & van Deursen, J. M. (2017) · Nature Reviews Nephrology · doi:10.1038/nrneph.2016.183 · Cited by 345
Mutant p53 Suppresses Innate Immune Signaling to Promote Tumorigenesis
Ghosh, M., Saha, S., Bettke, J. A., Nagar, R., Parrales, A., Iwakuma, T., van der Velden, A. W. M., & Martinez, L. A. (2020) · Cancer Cell · doi:10.1016/j.ccell.2021.01.003 · Cited by 355
p53, cancer and the immune response
Blagih, J., Buck, M. D., & Vousden, K. H. (2020) · Journal of Cell Science · doi:10.1242/jcs.237453 · Cited by 333
“This response attracts NK and myeloid cells that can function to remove damaged hepatocytes and so limit fibrosis, cirrhosis and HCC development (Krizhanovsky et al., 2008; Lujambio et al., 2013) (Fig.”
BackgroundEmerging roles of p53 and other tumour-suppressor genes in immune regulation
Muñoz‐Fontela, C., Mandinova, A., Aaronson, S. A., & Lee, S. W. (2016) · Nature reviews. Immunology · doi:10.1038/nri.2016.99 · Cited by 344
Liedtke, C., Luedde, T., Sauerbruch, T., Scholten, D., Streetz, K. L., Tacke, F., Tolba, R. H., Trautwein, C., Trebicka, J., & Weiskirchen, R. (2013) · Fibrogenesis & Tissue Repair · doi:10.1186/1755-1536-6-19 · Cited by 346
The post-translational modification, SUMOylation, and cancer (Review)
Han, Z., Feng, Y.-H., Gu, B.-H., Li, Y., & Chen, H. (2018) · International Journal of Oncology · doi:10.3892/ijo.2018.4280 · Cited by 358
“…chemokines, growth factors and matrix remodeling factors or matrix metalloproteinases, which alter the local tissue environment and contributes to chronic inflammation and cancer (201). p53 promotes cellular senescence, as well as programmed cell death (apoptosis) as a tumor suppressor (202).”
Tumor-Suppressor Functions of the TP53 PathwayPreprint
Aubrey, B. J., Strasser, A., & Kelly, G. L. (2016) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a026062 · Cited by 352
“For example, in a mouse model of hepatocellular carcinoma, TP53 was shown to influence the microenvironment and immune response via a non-tumor-cell-autonomous mechanism, which impacted the rate of tumor expansion and aggressiveness (Lujambio et al. 2013).”
BackgroundBorghesan, M., Fafián-Labora, J., Eleftheriadou, O., Carpintero-Fernández, P., Paez-Ribes, M., Vizcay-Barrena, G., Swisa, A., Kolodkin-Gal, D., Ximénez-Embún, P., Lowe, R., et al. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.05.095 · Cited by 315
“, 2017); and (3) ex vivo mouse hepatic stellate cells (mHSCs) derived from an adult mouse harboring a doxycycline (Dox)inducible construct to express shp53 (Krizhanovsky et al., 2008; Lujambio et al., 2013) (Figure S1L).”
BackgroundResultInhibitors of histone acetyltransferases KAT6A/B induce senescence and arrest tumour growth
Baell, J. B., Leaver, D. J., Hermans, S. J., Kelly, G. L., Brennan, M. S., Downer, N. L., Nguyen, N. H., Wichmann, J., McRae, H. M., Yang, Y., et al. (2018) · Nature · doi:10.1038/s41586-018-0387-5 · Cited by 321
p53 and Tumor Suppression: It Takes a Network
Boutelle, A. M., & Attardi, L. D. (2021) · Trends in Cell Biology · doi:10.1016/j.tcb.2020.12.011 · Cited by 335
Watanabe, S., Kawamoto, S., Ohtani, N., & Hara, E. (2017) · Cancer Science · doi:10.1111/cas.13184 · Cited by 321
Andoniadou, C. L., Matsushima, D., Mousavy-Gharavy, S. N., Signore, M., Mackintosh, A. I., Schaeffer, M., Gaston‐Massuet, C., Mollard, P., Jacques, T. S., Tissier, P. L., et al. (2013) · Cell stem cell · doi:10.1016/j.stem.2013.07.004 · Cited by 319
“Recently, a non-cell-autonomous effect of p53 was shown in a model of hepatocellular carcinoma, where p53-ablated hepatic stellate cells were able to induce tumors in a paracrine fashion (Lujambio et al., 2013).”
BackgroundUHRF1 Overexpression Drives DNA Hypomethylation and Hepatocellular Carcinoma
Mudbhary, R., Hoshida, Y., Chernyavskaya, Y., Jacob, V., Villanueva, A., Fiel, M. I., Chen, X., Kojima, K., Thung, S. N., Bronson, R. T., et al. (2014) · Cancer Cell · doi:10.1016/j.ccr.2014.01.003 · Cited by 310
“, 2007) and in hepatic stellate cells (Table S6; Figure S6C; Lujambio et al., 2013).”
BackgroundMethodInfluentialRecent advancement of molecular mechanisms of liver fibrosis
Seki, E., & Brenner, D. A. (2015) · Journal of Hepato-Biliary-Pancreatic Sciences · doi:10.1002/jhbp.245 · Cited by 302
“the polarization of liver macrophages to M1-state through their senescence-associated secretory phonotype (SASP), resulting in inhibiting the development of hepatocellular carcinoma (HCC) [48].”
BackgroundInfluentialRole of nonresolving inflammation in hepatocellular carcinoma development and progression
Yu, L., Yan, L., & Wang, H. (2018) · npj Precision Oncology · doi:10.1038/s41698-018-0048-z · Cited by 309
“A recent report showed that deletion of p53 in hepatic stellate cells led to the macrophage M2 polarization thus avoided immune elimination and resulted in accelerated HCC development in a DEN-induced HCC model.(100) Moreover, liver macrophages in the Fig.”
BackgroundCellular senescence in development, regeneration and disease
Rhinn, M., Ritschka, B., & Keyes, W. M. (2019) · Development · doi:10.1242/dev.151837 · Cited by 279
Ohtani, N. (2022) · Inflammation and Regeneration · doi:10.1186/s41232-022-00197-8 · Cited by 329
“SASP factors can also act in a paracrine manner, inducing senescence of surrounding cells, and this is termed as paracrine senescence [10].”
BackgroundAcute Promyelocytic Leukemia: A Paradigm for Oncoprotein-Targeted Cure
de Thé, H., Pandolfi, P. P., & Chen, Z. (2017) · Cancer Cell · doi:10.1016/j.ccell.2017.10.002 · Cited by 307
“In mouse models, senescence seems implicated in APL clearance, and the immune system is critically important to eliminate senescent cells (Ablain et al., 2014; Korf et al., 2014; Lujambio et al., 2013; Nardella et al., 2011).”
BackgroundGenetic and non-genetic clonal diversity in cancer evolution
Black, J. R., & McGranahan, N. (2021) · Nature reviews. Cancer · doi:10.1038/s41568-021-00336-2 · Cited by 298
Cuollo, L., Antonangeli, F., Santoni, A., & Soriani, A. (2020) · Biology · doi:10.3390/biology9120485 · Cited by 291
DNA damage response and metabolic disease
Shimizu, I., Yoshida, Y., Suda, M., & Minamino, T. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.10.008 · Cited by 286
The p53 network: cellular and systemic DNA damage responses in cancer and aging
Vaddavalli, P. L., & Schumacher, B. (2022) · Trends in Genetics · doi:10.1016/j.tig.2022.02.010 · Cited by 304
Cell fusion induced by ERVWE1 or measles virus causes cellular senescence
Chuprin, A., Gal, H., Biron-Shental, T., Biran, A., Amiel, A., Rozenblatt, S., & Krizhanovsky, V. (2013) · Genes & Development · doi:10.1101/gad.227512.113 · Cited by 262
“SASP components were shown to either inhibit or promote cancer progression in a cell-nonautonomous manner in different settings (Canino et al. 2012; Lujambio et al. 2013).”
BackgroundSelf-citationBird, T. G., Müller, M., Boulter, L., Vincent, D. F., Ridgway, R. A., Lopez-Guadamillas, E., Lu, W.-Y., Jamieson, T., Govaere, O., Campbell, A. D., et al. (2018) · Science Translational Medicine · doi:10.1126/scitranslmed.aan1230 · Cited by 261
“SASP may also modulate fibrosis and regeneration in response to acute tissue injury (11, 16, 17).”
Xiao, Y., Chen, J., Zhou, H., Zeng, X., Ruan, Z., Pu, Z., Jiang, X., Matsui, A., Zhu, L., Amoozgar, Z., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-28279-8 · Cited by 269
Macrophages in age-related chronic inflammatory diseases
Oishi, Y., & Manabe, I. (2016) · npj Aging and Mechanisms of Disease · doi:10.1038/npjamd.2016.18 · Cited by 262
“SASP factors secreted from hepatic stellate cells shift macrophage polarization from M2 toward M1.(75) Accordingly, it is likely that exogenous changes in the microenvironment (e.”
BackgroundInfluentialPhysiological and pathological consequences of cellular senescence
Burton, D. G. A., & Krizhanovsky, V. (2014) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-014-1691-3 · Cited by 253
“A recent study has shown that senescent HSCs can be eliminated by another component of the innate immune system, the M1-like macrophages during liver damage and tumorigenesis in the liver [89].”
BackgroundSelf-citationThe wound healing, chronic fibrosis, and cancer progression triad
Rybinski, B., Franco‐Barraza, J., & Cukierman, E. (2014) · Physiological Genomics · doi:10.1152/physiolgenomics.00158.2013 · Cited by 265
Malaquin, N., Martinez, A., & Rodier, F. (2016) · Experimental Gerontology · doi:10.1016/j.exger.2016.05.010 · Cited by 247
“, 2016)} and selective immune clearance have emerged as promising strategies to selectively eliminate senescent cells (Kang et al., 2011; Lujambio et al., 2013; Xue et al., 2007).”
Senescent cells: SASPected drivers of age-related pathologies
Ovadya, Y., & Krizhanovsky, V. (2014) · Biogerontology · doi:10.1007/s10522-014-9529-9 · Cited by 232
“Senescent hepatic stellate cells (HSCs) release SASP factors such as IFN-c and IL-6 that skew macrophage toward the M1 state during liver disease (Lujambio et al. 2013).”
BackgroundSelf-citationDurán, Á., Hernandez, E. D., Reina‐Campos, M., Castilla, E. A., Subramaniam, S., Raghunandan, S., Roberts, L. R., Kisseleva, T., Karin, M., Díaz-Meco, M. T., et al. (2016) · Cancer Cell · doi:10.1016/j.ccell.2016.09.004 · Cited by 243
“…in GFAP-Cre mice was reported to result in three outcomes: (1) recombination only in HSCs (Kisseleva and Brenner, 2008; Krizhanovsky et al., 2008; Lujambio et al., 2013); (2) recombination only in cholangiocytes (Mederacke et al., 2013); and (3) recombination in both HSCs and cholangiocytes…”
Influentialp53-Dependent Nestin Regulation Links Tumor Suppression to Cellular Plasticity in Liver Cancer
Tschaharganeh, D. F., Xue, W., Calvisi, D. F., Evert, M., Michurina, T. V., Dow, L. E., Banito, A., Katz, S. F., Kastenhuber, E. R., Weissmueller, S., et al. (2014) · Cell · doi:10.1016/j.cell.2014.05.051 · Cited by 227
Self-citationThe current paradigm and challenges ahead for the dormancy of disseminated tumor cells
Risson, E., Nobre, A. R., Maguer‐Satta, V., & Aguirre‐Ghiso, J. A. (2020) · Nature Cancer · doi:10.1038/s43018-020-0088-5 · Cited by 248
Cellular senescence: Immunosurveillance and future immunotherapy
Burton, D. G. A., & Stolzing, A. (2018) · Ageing Research Reviews · doi:10.1016/j.arr.2018.02.001 · Cited by 221
“This study demonstrated that p53-expressing senescent stellate cells release factors which promote macrophage polarisation towards a tumour-inhibiting M1 state capable of targeting senescent cells in cultures (Lujambio et al., 2013).”
Background
Metadata
- Authors
- Lujambio, A., Akkari, L., Simon, J., Grace, D., Tschaharganeh, D. F., Bolden, J. E., Zhao, Z., Thapar, V., Joyce, J. A., Krizhanovsky, V., & Lowe, S. W.
- Affiliations
- Memorial Sloan Kettering Cancer Center (US)
- Cold Spring Harbor Laboratory (US)
- Corresponding author
- Krizhanovsky, Valery
- Lowe, Scott W.
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2013-04
- Volume
- 153
- Issue
- 2
- Pages
- 449-460
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC3702034
- OpenAlex
- W2104397341
- Cited by
- 766
- References
- 48
- Citations by year
- 2026: 35 · 2025: 67 · 2024: 61 · 2023: 52 · 2022: 66 · 2021: 74 · 2020: 70 · 2019: 51 · 2018: 62 · 2017: 57 · 2016: 49 · 2015: 47 · 2014: 46 · 2013: 28
- FWCI
- 39.35
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) (submittedVersion)
- Swinburne figshare (Swinburne University of Technology) (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- Memorial Sloan-Kettering Cancer Center
- Cold Spring Harbor Laboratory
- Deutsche Forschungsgemeinschaft
- Weizmann Institute of Science
- Israel Science Foundation
- National Institute on Aging (R56AG016379, AG-16379, R01AG016379)
- National Cancer Institute (P01CA087497, U54CA148967, P01CA013106, P30CA008748)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Keywords
- p53, cellular senescence, hepatic stellate cells, liver fibrosis, liver cirrhosis, hepatocellular carcinoma, macrophage polarization, M1/M2 macrophages, tumor microenvironment, chronic liver injury, premalignant cells, secreted factors
- MeSH terms
- Animals, Cell Transformation, Neoplastic, Fibrosis, Humans, Inflammation, Kupffer Cells, Liver, Liver Neoplasms, Macrophages, Tumor Suppressor Protein p53, NF-kappa B, Cellular Senescence, Mice, Hepatic Stellate Cells, Cellular Microenvironment
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