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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
“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
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 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]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“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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In the citing paper
“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
“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]
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
“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]
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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“In the presence of chronic liver damage, disruption of the p53-dependent senescence program in HSCs increases liver fibrosis and cirrhosis leading to reduced survival and enhanced transformation of adjacent epithelial cells (Lujambio et al. 2013).”
BackgroundInfluentialSelf-citationSASP: Tumor Suppressor or Promoter? Yes!
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“A study reports that p53 can inhibit malignant transformation by triggering the cell‐autonomous program of apoptosis or cell‐ cycle arrest and noncell autonomous program of cellular senescence through secreted factors that regulate the macrophage function (Lujambio et al., 2013).”
BackgroundStrategies targeting cellular senescence
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Self-citationIntegrin Beta 3 Regulates Cellular Senescence by Activating the TGF-β Pathway
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“We also emphasize that while specificity of human GFAP-Cre expression has been questioned [25], both this study and separate reports [12, 13] underscore its utility to drive stellate cell cre expression.”
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BackgroundInfluentialSenescence in Wound Repair: Emerging Strategies to Target Chronic Healing Wounds
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“initiates cellular senescence of surrounding non-senescent HSCs (Lujambio et al., 2013; Sugihara et al., 2018).”
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“We also observed significant reduction of P53-signaling–related genes, suggesting cell death evasion (24, 25).”
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“…proteases (the senescence-associated secretory phenotype [SASP]) (Krtolica et al. 2001; Acosta et al. 2008; Kuilman et al. 2008), can also contribute to tumor suppression by promoting clearance of some senescent cells by the immune system (Xue et al. 2007; Kang et al. 2011; Lujambio et al. 2013).”
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“On the other hand, another report showed that the suppression of cellular senescence in HSCs by crossing p53flox/flox and GFAP (glial fibrillary acidic protein)–Cre mice exhibited subtle increase of HCC development (56), suggesting a tumor-suppressive role of SASP in HSCs.”
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“Recent studies showed that targeted p53 activation/restoration via genetic approach activates NK cells and macrophages (15,16).”
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“secretory phenotypes can contribute to tumor suppression in a non-cell-autonomous manner, for instance, controlling the inflammatory microenvironment and promoting macrophage M1- versus M2-type polarization (Lowe et al., 2013; Lujambio et al., 2013; Schwitalla et al., 2013).”
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“Of note, the p53 status of the hepatic stellate cells affected the macrophage polarization in the tissue, tilting it toward the M1 proinflammatory program in the presence of WTp53 while favoring the M2 tumor-promoting phenotype in the absence of p53 (161).”
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“Additionally, the TP53 gene suppresses tumorigenesis by determining DNA damage repair or apoptosis of damaged cells, promoting a tumor-inhibiting microenvironment through modulating macrophage polarization towards M1-state [59] and remodeling myeloid-T cell crosstalk [50].”
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“In addition, these subgroups largely corresponded to HSC activation status as determined by hierarchical clustering of common HSC activation markers, i.e., ATCA2, COL1A1, COL1A2, TIMP1, and SPARC.24,25 The activation of HSCs was observed in a majority of high-risk cases (74%; Fig.”
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“For example, during liver fibrosis, p53-expressing senescent liver satellite cells release IFN-c and IL-6, which in turn skew the polarization of resident Kupffer macrophages and freshly infiltrated macrophages toward the proinflammatory M1 phenotype (Lujambio et al., 2013).”
BackgroundInfluentialThe p53 family and the hypoxia-inducible factors (HIFs): determinants of cancer progression
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“non–cell autonomous behaviors during tumorigenesis (22, 23).”
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“other components of the innate immune system, including natural killer (NK) cells, neutrophils, dendritic cells, and macrophages, functionally contribute to elimination of senescent cells (11, 15, 21).”
BackgroundTeng, Y., Mu, J., Hu, X., Samykutty, A. K., Zhuang, X., Deng, Z., Zhang, L., Cao, P., Yan, J., Miller, D. M., et al. (2016) · Oncotarget · doi:10.18632/oncotarget.8361 · Cited by 139
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How mutations shape p53 interactions with the genome to promote tumorigenesis and drug resistance
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Inhibition of p53 inhibitors: progress, challenges and perspectives
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“cells, screw macrophage polarization towards tumor-inhibiting M1 state (Lujambio et al., 2013).”
BackgroundWang, L., Cao, Z., Zhang, M., Lin, S., & Liu, J. (2021) · Advanced Materials · doi:10.1002/adma.202106669 · Cited by 140
Senescence and the tumor-immune landscape: Implications for cancer immunotherapy
Chibaya, L., Snyder, J. T., & Ruscetti, M. A. (2022) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2022.02.005 · Cited by 146
Cancer and Aging - the Inflammatory Connection
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“Proc Natl Acad Sci U S A, 98: 12072-12077 [82] Lujambio A, Akkari L, Simon J, Grace D,”
BackgroundCui, Y. R., & Guo, G. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms17111942 · Cited by 137
“Recently, compelling evidence demonstrates that p53 also suppresses tumorigenesis via changing the function and milieu of the transformed cells, which is regarded as the non-cell autonomous mechanism of tumor suppression [32,33].”
BackgroundTargeting Cardiac Stem Cell Senescence to Treat Cardiac Aging and Disease
Cianflone, E., Torella, M., Biamonte, F., Angelis, A. D., Urbanek, K., Costanzo, F. S., Rota, M., Ellison, G. M., & Torella, D. (2020) · Cells · doi:10.3390/cells9061558 · Cited by 137
Lesina, M., Wörmann, S. M., Morton, J. P., Diakopoulos, K. N., Korneeva, O., Wimmer, M., Einwächter, H., Sperveslage, J., Demir, İ. E., Kehl, T., et al. (2016) · Journal of Clinical Investigation · doi:10.1172/jci86477 · Cited by 134
“RelA has been shown to cooperate with p53 in the execution of the senescence program (36).”
BackgroundMacrophage biology plays a central role during ionizing radiation-elicited tumor response
Wu, Q., Allouch, A., Martins, I., Modjtahedi, N., Deutsch, É., & Perfettini, J. (2017) · Biomedical Journal · doi:10.1016/j.bj.2017.06.003 · Cited by 136
“[57] Lujambio A, Akkari L, Simon J, Grace D, Tschaharganeh DF, Bolden JE, et al.”
BackgroundSenolytics for Cancer Therapy: Is All that Glitters Really Gold?
Carpenter, V. J., Saleh, T., & Gewirtz, D. A. (2021) · Cancers · doi:10.3390/cancers13040723 · Cited by 124
The types of hepatic myofibroblasts contributing to liver fibrosis of different etiologies
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“…recombination Frontiers in Pharmacology | Inflammation Pharmacology July 2014 | Volume 5 | Article 167 | 2 in HSCs (Kisseleva and Brenner, 2008a; Krizhanovsky et al., 2008; Lujambio et al., 2013), in cholangiocytes (Mederacke et al., 2013), or in both HSCs and cholangiocytes (Yang et al., 2008).”
BackgroundXiang, D., Zou, J., Zhu, X., Chen, X., Luo, J., Kong, L., & Zhang, H. (2020) · Phytomedicine · doi:10.1016/j.phymed.2020.153294 · Cited by 123
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Of Flies, Mice, and Men: Evolutionarily Conserved Tissue Damage Responses and Aging
Neves, J., Demaria, M., Campisi, J., & Jasper, H. (2015) · Developmental Cell · doi:10.1016/j.devcel.2014.11.028 · Cited by 119
“In a model of liver cancer due to fibrosis and cirrhosis, a p53-dependent senescence program in hepatic stellate cells promotes an antitumor microenvironment through the differentiation of macrophages toward tumor-inhibiting functions (Lujambio et al., 2013).”
BackgroundThe Paradoxical Role of Cellular Senescence in Cancer
Yang, J., Liu, M., Hong, D., Zeng, M., & Zhang, X. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.722205 · Cited by 125
Vilgelm, A. E., Pawlikowski, J. S., Liu, Y., Hawkins, O. E., Davis, T. A., Smith, J., Weller, K. P., Horton, L. W., McClain, C. M., Ayers, G. D., et al. (2015) · Cancer Research · doi:10.1158/0008-5472.can-14-2405 · Cited by 115
Lunyak, V. V., Amaro-Ortiz, A., & Gaur, M. (2017) · Frontiers in Genetics · doi:10.3389/fgene.2017.00220 · Cited by 119
Cellular senescence: a double-edged sword in cancer therapy
Xiao, S., Qin, D., Hou, X., Tian, L., Yu, Y., Zhang, R., Lyu, H., Guo, D. S., Chen, X., Zhou, C., et al. (2023) · Frontiers in Oncology · doi:10.3389/fonc.2023.1189015 · Cited by 128
“Senescent cells persistently secrete various SASP factors through the paracrine pathway to affect adjacent tissues, which plays the most important role in pro-tumorigenesis (43).”
BackgroundInfluentialCell senescence in liver diseases: pathological mechanism and theranostic opportunity
Sanfeliu-Redondo, D., Gibert-Ramos, A., & Gracia-Sancho, J. (2024) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-024-00913-4 · Cited by 117
“Senescent HSCs also acquire a pro-inflammatory phenotype, promoting immune surveillance 93 .”
Can Targeting Stroma Pave the Way to Enhanced Antitumor Immunity and Immunotherapy of Solid Tumors?
Puré, E., & Lo, A. (2016) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-16-0011 · Cited by 112
p53 on the crossroad between regeneration and cancer
Charni‐Natan, M., Aloni-Grinstein, R., Molchadsky, A., & Rotter, V. (2016) · Cell Death and Differentiation · doi:10.1038/cdd.2016.117 · Cited by 115
“These agents can cause long-term damage that may lead to liver fibrosis and even to liver cirrhosis, which eventually may result in HCC.76 Chronic injuries lead to reduction of hepatocytes proliferative capacity, inducing them to undergo senescence, mediated by p53.”
BackgroundInfluentialMesothelin/mucin 16 signaling in activated portal fibroblasts regulates cholestatic liver fibrosis
Koyama, Y., Wang, P., Liang, S., Iwaisako, K., Liu, X., Xu, J., Zhang, M., Sun, M., Cong, M., Karin, D., et al. (2017) · Journal of Clinical Investigation · doi:10.1172/jci88845 · Cited by 115
“Although the origin of aPFs during development has been identified in embryonic mesenchyme (32), which is also rich in MSLN expression (31, 53), the source of proliferating aPFs in the adult injured murine liver remains unclear.”
Arandkar, S., Furth, N., Elisha, Y., Nataraj, N. B., van der Kuip, H., Yarden, Y., Aulitzky, W. E., Ulitsky, I., Geiger, B., & Oren, M. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1719076115 · Cited by 115
“While the cell-autonomous and nonautonomous tumor-suppressive functions of p53 in NFs have been studied in detail (9, 15, 16), its impact on the properties of CAFs is less well established.”
BackgroundReshaping of the tumor microenvironment by cellular senescence: An opportunity for senotherapies
D’Ambrosio, M., & Gil, J. (2023) · Developmental Cell · doi:10.1016/j.devcel.2023.05.010 · Cited by 111
The hepatitis B virus-associated tumor microenvironment in hepatocellular carcinoma
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“IL-6 exhibits potent pro-tumorigenic effects such as modulation of proliferation, and survival of hepatocytes and differentiation of Th17 cells, a T-cell subpopulation whose accumulation has been correlated with microvessel density and poor prognosis in HCC patients [99,104–109].”
BackgroundMutant p53: Multiple Mechanisms Define Biologic Activity in Cancer
Kim, M., Zhang, Y., & Lozano, G. (2015) · Frontiers in Oncology · doi:10.3389/fonc.2015.00249 · Cited by 113
“Lujambio and colleagues selectively deleted p53 in hepatic stellate cells, resulting in modifications to the tumor microenvironment (TME) and enhanced malignant transformation of epithelial cells (59).”
BackgroundTargeting senescence as an anticancer therapy
Bousset, L., & Gil, J. (2022) · Molecular Oncology · doi:10.1002/1878-0261.13312 · Cited by 113
Regulation of senescence and the SASP by the transcription factor C/EBPβ
Salotti, J., & Johnson, P. F. (2019) · Experimental Gerontology · doi:10.1016/j.exger.2019.110752 · Cited by 103
Nelson, D. M., Jaber‐Hijazi, F., Cole, J. J., Robertson, N., Pawlikowski, J. S., Norris, K., Criscione, S. W., Pchelintsev, N. A., Piscitello, D., Stong, N., et al. (2016) · Genome biology · doi:10.1186/s13059-016-1017-x · Cited by 105
The ubiquitin ligase MDM2 sustains STAT5 stability to control T cell-mediated antitumor immunity
Zhou, J., Kryczek, I., Li, S., Xiong, L., Aguilar, A., Wei, S., Grove, S., Vatan, L., Yu, J., Yan, Y., et al. (2021) · Nature Immunology · doi:10.1038/s41590-021-00888-3 · Cited by 107
To clear, or not to clear (senescent cells)? That is the question
Lujambio, A. (2016) · BioEssays · doi:10.1002/bies.201670910 · Cited by 108
Self-citationSenescent cells and macrophages: key players for regeneration?
Elder, S. S., & Emmerson, E. (2020) · Open Biology · doi:10.1098/rsob.200309 · Cited by 114
“However, in senescent stellate cells lacking p53, IL-4 was produced, causing macrophage polarization towards the pro-survival M2 phenotype [119].”
BackgroundStellate Cells in Tissue Repair, Inflammation, and Cancer
Sherman, M. H. (2018) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-100617-062855 · Cited by 104
Targeting YAP-mediated HSC death susceptibility and senescence for treatment of liver fibrosis
Du, K., Maeso-Díaz, R., Oh, S. H., Wang, E., Chen, T., Pan, C., Xiang, K., Dutta, R. K., Wang, X.-F., Chi, J.-T., et al. (2023) · Hepatology · doi:10.1097/hep.0000000000000326 · Cited by 102
“[3] However, while many studies reported that HSC senescence limits liver fibrosis,[4,5] many others claimed that it favors fibrosis progression and leads to liver cancer through the SASP secretome.”
BackgroundCOX2 regulates senescence secretome composition and senescence surveillance through PGE2
Gonçalves, S., Yin, K., Ito, Y., Chan, A., Olan, I., Gough, S., Cassidy, L., Serrao, E., Smith, S., Young, A., et al. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.108860 · Cited by 95
“, 2018), macrophages (Eggert et al., 2016; Kang et al., 2011; Lujambio et al., 2013) and natural killer (NK) cells (Sagiv et al.”
BackgroundLade, A. G., Noon, L. A., & Friedman, S. L. (2013) · Current Opinion in Oncology · doi:10.1097/cco.0000000000000042 · Cited by 103
P53: A Guardian of Immunity Becomes Its Saboteur through Mutation
Agupitan, A. D., Neeson, P. J., Williams, S., Howitt, J. A., Haupt, S., & Haupt, Y. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21103452 · Cited by 111
“The loss of wt p53 activity in CAFs can further exert selective pressure to promote transformation in neighbouring epithelial cells through ablation of p53-dependent senescence programs and skewed macrophage polarisation (Figure 2B) [91].”
BackgroundMolecular pathways of senescence regulate placental structure and function
Gal, H., Lysenko, M., Stroganov, S., Vadai, E., Youssef, S. A., Geffen, K. T., Rotkopf, R., Biron‐Shental, T., de Bruin, A., Neeman, M., et al. (2019) · The EMBO Journal · doi:10.15252/embj.2018100849 · Cited by 103
“The SASP, composed of pro-inflammatory cytokines, chemokines, growth factors, and proteases, can modulate the senescent cell’s microenvironment and promote its interaction with the immune system (Coppe et al , 2008; Lujambio et al , 2013; Sagiv & Krizhanovsky, 2013; Sagiv et al , 2016).”
Self-citationCellular senescence in gastrointestinal diseases: from pathogenesis to therapeutics
Frey, N., Venturelli, S., Zender, L., & Bitzer, M. (2018) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2017.146 · Cited by 97
Cell fate regulation governed by p53: Friends or reversible foes in cancer therapy
Song, B., Yang, P., & Zhang, S. (2024) · 癌症：英文版 · doi:10.1002/cac2.12520 · Cited by 103
The role of MDM2–p53 axis dysfunction in the hepatocellular carcinoma transformation
Cao, H., Chen, X., Wang, Z., Wang, L., Xia, Q., & Zhang, W. (2020) · Cell Death Discovery · doi:10.1038/s41420-020-0287-y · Cited by 93
Cellular senescence: from growth arrest to immunogenic conversion
Burton, D. G. A., & Faragher, R. (2015) · AGE · doi:10.1007/s11357-015-9764-2 · Cited by 99
“In another study, senescent hepatic stellate cells secreted factors that favoured macrophage polarization towards a tumour-inhibiting M1-state capable of targeting senescent cells (Lujambio et al. 2013).”
BackgroundKolodkin‐Gal, D., Roitman, L., Ovadya, Y., Azazmeh, N., Assouline, B., Schlesinger, Y., Kalifa, R., Horwitz, S., Khalatnik, Y., Hochner-Ger, A., et al. (2021) · Gut · doi:10.1136/gutjnl-2020-321112 · Cited by 93
Self-citationFASN activity is important for the initial stages of the induction of senescence
Fafián‐Labora, J., Carpintero-Fernández, P., Jordan, S. J. D., Shikh-Bahaei, T., Abdullah, S. M., Mahenthiran, M., Rodríguez‐Navarro, J. A., Niklison-Chirou, M. V., & O’Loghlen, A. (2019) · Cell Death and Disease · doi:10.1038/s41419-019-1550-0 · Cited by 91
The role of senescence in cancer development
Mavrogonatou, E., Pratsinis, H., & Kletsas, D. (2019) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2019.06.018 · Cited by 95
Can blocking inflammation enhance immunity during aging?
Chambers, E. S., & Akbar, A. N. (2020) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2020.03.016 · Cited by 92
“Senescence is a protective process that prevents the proliferation of damaged cells and is viewed as a tumour suppressor mechanism (48, 49).”
BackgroundTargeting cellular senescence in cancer and aging: roles of p53 and its isoforms
Beck, J. A., Turnquist, C., Horikawa, I., & Harris, C. C. (2020) · Carcinogenesis · doi:10.1093/carcin/bgaa071 · Cited by 97
“This is thought to be due to the loss of critical functions mediated by senescent stellate cells such as promotion of antitumor macrophages and inhibition of hepatocyte transformation (59).”
BackgroundInfluential
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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