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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.
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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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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
Cites
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“During liver fibrosis, for example, p53-expressing senescent liver satellite cells produce IFN- and IL-6, skewing the polarization of resident Kupffer macrophages and newly recruited macrophages toward the proinflammatory M1 phenotype [89].”
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Macrophage Involvement in Aging-Associated Skeletal Muscle Regeneration
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Antifibrotic therapies for metabolic dysfunction-associated steatotic liver disease
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“103 Senescence limits their ability to proliferate and produce ECM and can thereby reduce further expansion and fi brosis, 104,105 as well as long-term consequences such as the development of HCC. 106 However, senescent HSCs are also characterised by an increased expression of in fl ammatory mediators, termed the senesc…”
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“A non-cell autonomous mechanism of tumor suppression by p53 has been described through skewing of macrophage polarization toward the tumor-inhibiting M1subtype; selective p53 deletion in the myeloid lineage led to elevated levels of inflammatory cytokines and a significant increase in tumor initiation whereas mild act…”
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“…fibrosis in response to chemical-induced or physical injury, modulation of the immune response and transmission of senescence to normal neighbouring cells adjacent to senescent lesions (Acosta et al., 2013; Jun and Lau, 2010; Krizhanovsky et al., 2008; Lujambio et al., 2013; Nelson et al., 2012).”
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Mechanisms involved in hematopoietic stem cell aging
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“A recent study shows that P53-expressing senescent cells secrete factors that promote macrophage activation towards tumor-inhibiting M1-state, whereas P53-deficient cells secrete those that skew macrophage activation towards tumor-promoting M2-state (45).”
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“In these patients, the accumulation of inflammatory cells likely contributes to the malignant potential of cancer cells and HCC formation [5].”
Markov state models and NMR uncover an overlooked allosteric loop in p53
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“In a fibrosis-associated liver cancer model, SASP facilitated macrophage polarization to an M1 state, capable of attacking senescent cells in culture, contributing to an antitumor micro-environment.(42) In contrast, the persistent presence of SASP factors is harmful and promotes tumorigenesis, inducing chronic inflamm…”
BackgroundComplement System in Cutaneous Squamous Cell Carcinoma
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Self-citationRecent advances in age-related metabolic dysfunction-associated steatotic liver disease
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“Conversely, a study has found that p53-knockout hepatic stellate cells promote macrophage differentiation towards the pro-tumor M2 phenotype, thereby inducing the progression of liver fibrosis, cirrhosis, and even HCC[12].”
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“In a p53-dependent manner, senescent hepatic stellate cells secrete factors that skew macrophage polarization towards a pro-inflammatory M1 type, which then contributes to tumour suppression (Lujambio et al., 2013).”
BackgroundEiger/TNFα-mediated Dilp8 and ROS production coordinate intra-organ growth in Drosophila
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“In fact, the modulation of inflammatory cytokine secretion by tumor-mediated activation of p53 has been shown to limit tissue damage [8], inhibit adjacent epithelial cell transformation [4], and promote macrophage-mediated clearance of tumor and apoptotic cells [9,10].”
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“Senescent HSCs have been shown to secrete a SASP [58] and stimulate M1-polarized macrophages [59].”
BackgroundWong, G. C., & Chow, H. (2022) · Journal of Alzheimer s Disease · doi:10.3233/jad-220203 · Cited by 41
M1 macrophage dependent-p53 regulates the intracellular survival of mycobacteria
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A protumorigenic secretory pathway activated by p53 deficiency in lung adenocarcinoma
Tan, X., Shi, L., Banerjee, P., Liu, X., Guo, H., Yu, J., Bota‐Rabassedas, N., Rodriguez, B. L., Gibbons, D. L., Russell, W. K., et al. (2020) · Journal of Clinical Investigation · doi:10.1172/jci137186 · Cited by 40
“p53 deficiency in hepatic stellate cells releases factors that stimulate macrophage polarization into a tumor-promoting M2 state and enhances the proliferation of premalignant hepatic epithelial cells (32).”
BackgroundDeng, L., He, K., Pan, Y., Wang, H., Luo, Y., & Xia, Q. (2021) · International Journal of Medical Sciences · doi:10.7150/ijms.56003 · Cited by 36
“In liver, cellular senescence mechanism is associated with inhibition of liver cancer progression [17, 18].”
BackgroundNoh, J.-W., Yang, H.-K., Jun, M.-S., & Lee, B.-C. (2022) · Biomedicines · doi:10.3390/biomedicines10010175 · Cited by 39
“TP53 expression stimulates macrophage polarization in the M2state [19].”
BackgroundSenescence of Tumor Cells in Anticancer Therapy—Beneficial and Detrimental Effects
Piskorz, W. M., & Cechowska‐Pasko, M. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms231911082 · Cited by 39
“Moreover, it can skew the polarity of macrophages to tumor-inhibiting state (M1), creating an antitumor environment [48].”
BackgroundMeng, Q., Luo, X., Chen, J., Wang, D., Chen, E., Zhang, W., Zhang, G., Zhou, W., Xu, J., & Song, Z. (2020) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2020.188443 · Cited by 38
The role of p53 in liver fibrosis
Yu, S., Ji, G., & Zhang, L. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.1057829 · Cited by 40
Zhang, X., Ng, Y. E., Chini, L., Heeren, A. A., White, T. A., Li, H., Huang, H., Doolittle, M. L., Khosla, S., & LeBrasseur, N. K. (2023) · Aging Cell · doi:10.1111/acel.14069 · Cited by 39
“It is commonly reported that the SASP promotes the proliferation and M1 polarization of macrophages (Irvine et al., 2014; Kale et al., 2020; Lujambio et al., 2013).”
BackgroundThe tumor immune microenvironment in gastroenteropancreatic neuroendocrine neoplasms
Zhang, W.-H., Wang, W., Gao, H.-L., Yu, X., & Liu, L. (2019) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2019.188311 · Cited by 38
Tao, Y., Shi, Y., Jia, J., Jiang, Y., Yang, L., & Cao, Y. (2015) · Expert Reviews in Molecular Medicine · doi:10.1017/erm.2015.13 · Cited by 36
Runx3 in Immunity, Inflammation and Cancer
Lotem, J., Levanon, D., Negreanu, V., Bauer, O., Hantisteanu, S., Dicken, J., & Groner, Y. (2017) · Advances in experimental medicine and biology · doi:10.1007/978-981-10-3233-2_23 · Cited by 38
Desumoylase SENP6 maintains osteochondroprogenitor homeostasis by suppressing the p53 pathway
Li, J., Lü, D., Dou, H., Liu, H., Weaver, K., Wang, W., Li, J., Yeh, E. T. H., Williams, B. O., Zheng, L., et al. (2018) · Nature Communications · doi:10.1038/s41467-017-02413-3 · Cited by 39
Aging tumour cells to cure cancer: “pro-senescence” therapy for cancer
Calcinotto, A., & Alimonti, A. (2017) · Swiss Medical Weekly · doi:10.57187/smw.2017.14367 · Cited by 42
Dying to Survive—The p53 Paradox
Lees, A., Sessler, T., & McDade, S. S. (2021) · Cancers · doi:10.3390/cancers13133257 · Cited by 38
Sun, D., Singh, D. K., Carcamo, S., Filipescu, D., Khalil, B. D., Huang, X., Miles, B. A., Westra, W. H., Sproll, K. C., Hasson, D., et al. (2022) · Science Advances · doi:10.1126/sciadv.abo0876 · Cited by 37
Insights into the role of senescence in tumor dormancy: mechanisms and applications
DeLuca, V. J., & Saleh, T. (2023) · Cancer and Metastasis Reviews · doi:10.1007/s10555-023-10082-6 · Cited by 37
“demonstrated this phenomenon in a model of chronic liver damage and tumorigenesis, in which p53 status of the senescent cells determined whether the SASP led to M1 or M2 polarization of resident macrophages [193].”
BackgroundCross-Talk Between Cancer and Its Cellular Environment—A Role in Cancer Progression
Turlej, E., Domaradzka, A., Radzka, J., Drulis‐Fajdasz, D., Kulbacka, J., & Gizak, A. (2025) · Cells · doi:10.3390/cells14060403 · Cited by 47
Vétillard, A., Jonchère, B., Moreau, M., Toutain, B., Henry, C., Fontanel, S., Bernard, A.-C., Campone, M., Guette, C., & Coqueret, O. (2015) · Oncotarget · doi:10.18632/oncotarget.6126 · Cited by 40
“It has been shown that efficient tumor suppression relies on senescent cells being cleared by immune cells [4-6].”
Dibra, D., Xia, X., Mitra, A., Cutrera, J., Lozano, G., & Li, S.-L. (2016) · Hepatology · doi:10.1002/hep.28379 · Cited by 30
“Meanwhile, another group has shown that p53 expression in activated stellate cells will limit liver fibrosis by inducing cell death of these cells.((14)) Because the role of mutant p53 in inflammation is so poorly understood, one imminent question is whether endogenous mutant p53 has any effect in liver inflammation a…”
BackgroundKumar, R., Sharma, A., Padwad, Y. S., & Sharma, R. (2020) · Biogerontology · doi:10.1007/s10522-020-09861-3 · Cited by 36
Autophagy inhibition signals through senescence to promote tumor suppression
Peng, N., Kang, H. H., Feng, Y., Minikes, A. M., & Jiang, X. (2022) · Autophagy · doi:10.1080/15548627.2022.2155794 · Cited by 37
NGAL as a Potential Target in Tumor Microenvironment
Crescenzi, E., Leonardi, A., & Pacifico, F. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222212333 · Cited by 34
Rappold, P. M., Vuong, L. H., Leibold, J., Chakiryan, N. H., Curry, M., Kuo, F., Sabio, E. Y., Jiang, H., Nixon, B. G., Liu, M., et al. (2022) · Cancer Discovery · doi:10.1158/2159-8290.cd-21-0925 · Cited by 36
“Several studies in autochthonous mouse models(75–77) suggest a direct role of tumor cell p53 loss in immunosuppressive myeloid recruitment, differentiation and function.”
BackgroundSelf-citationp53 and Myofibroblast Apoptosis in Organ Fibrosis
McElhinney, K., Irnaten, M., & O'Brien, C. J. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24076737 · Cited by 37
MicroRNAs and lncRNAs in senescence: A re‐view
Bischof, O., & Martínez‐Zamudio, R. I. (2015) · IUBMB Life · doi:10.1002/iub.1373 · Cited by 35
Notch1 -Induced Brain Tumor Models the Sonic Hedgehog Subgroup of Human Medulloblastoma
Natarajan, S., Li, Y., Miller, E. E., Shih, D. J. H., Taylor, M. D., Stearns, T. M., Bronson, R. T., Ackerman, S. L., Yoon, J. K., & Yun, K. (2013) · Cancer Research · doi:10.1158/0008-5472.can-13-0033 · Cited by 34
“This observations suggests a hitand-run or some other mechanism of oncogenesis by N1ICD that does not require sustained expression ofN1ICD in growing tumor cells, such as non–cell-autonomous effect of p53 recently reported (43).”
BackgroundShibamoto, M., Higo, T., Naito, A. T., Nakagawa, A., Sumida, T. S., Okada, K., Sakai, T., Kuramoto, Y., Yamaguchi, T., Ito, M., et al. (2019) · International Heart Journal · doi:10.1536/ihj.18-701 · Cited by 36
Siljamäki, E., Rappu, P., Riihilä, P., Nissinen, L. M., Kähäri, V., & Heino, J. (2019) · Matrix Biology · doi:10.1016/j.matbio.2019.09.001 · Cited by 35
Tumor suppressor p53 regulates intestinal type 2 immunity
Chang, C., Wang, J., Zhao, Y., Liu, J., Yang, X. F., Yue, X., Wang, H., Zhou, F., Inclan-Rico, J. M., Ponessa, J. J., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-23587-x · Cited by 35
p53 loss activates prometastatic secretory vesicle biogenesis in the Golgi
Tan, X., Banerjee, P., Shi, L., Xiao, G.-Y., Rodriguez, B. L., Grzeskowiak, C. L., Liu, X., Jiang, Y. L., Gibbons, D. L., Russell, W. K., et al. (2021) · Science Advances · doi:10.1126/sciadv.abf4885 · Cited by 35
“For example, p53 loss relieves cancer cells from senescence-related secreted factors that restrict angiogenesis and fibrosis and skew macrophage polarization toward the tumor-fighting M1-like state (39).”
BackgroundMutant p53—a potential player in shaping the tumor–stroma crosstalk
Stein, Y., Aloni-Grinstein, R., & Rotter, V. (2019) · Journal of Molecular Cell Biology · doi:10.1093/jmcb/mjz071 · Cited by 35
Ets2 anchors the prometastatic function of mutant p53 in osteosarcomaPreprint
Liu, D. D., & Kang, Y. (2017) · Genes & Development · doi:10.1101/gad.307439.117 · Cited by 34
“This is a particularly salient concern, as p53 is known to exert non-cell-autonomous effects via stromal cells (Lujambio et al. 2013).”
BackgroundContext‐dependent roles of cellular senescence in normal, aged, and disease states
Moiseeva, V., Cisneros, A., Cobos, A. C., Tarrega, A. B., Oñate, C. S., Perdiguero, E., Serrano, A. L., & Muñoz‐Cánoves, P. (2023) · The FEBS Journal · doi:10.1111/febs.16573 · Cited by 34
Insights Into Mechanisms of Tumor and Immune System Interaction: Association With Wound Healing
Ponomarev, А. V., & Shubina, I. Z. (2019) · Frontiers in Oncology · doi:10.3389/fonc.2019.01115 · Cited by 36
“At the same time, proliferating p53-deficient stellate cells secrete factors that stimulate macrophage polarization to M2 phenotype (172).”
BackgroundMutant P53 in the formation and progression of the tumor microenvironment: Friend or foe
Asl, E. R., Rostamzadeh, D., Duijf, P. H. G., Mafi, S., Mansoori, B., Barati, S., Cho, W. C. S., & Mansoori, B. (2023) · Life Sciences · doi:10.1016/j.lfs.2022.121361 · Cited by 38
Fu, Y., Guo, X., Sun, L., Cui, T., Wu, C., Wang, J., Liu, Y., & Liu, L. (2024) · eLife · doi:10.7554/elife.95009 · Cited by 31
“Moreover, the data suggest that because of tumor heterogeneity, targeting the TME may be a more effective strategy than targeting tumor cells ( Lujambio et al., 2013 ; Zhu et al., 2022 ).”
BackgroundGómez‐Santos, B., de Urturi, D. S., Núñez-García, M., González‐Romero, F., Buqué, X., Aurrekoetxea, I., de Juan, V. G., Gonzalez-Rellan, M. J., García‐Monzón, C., González‐Rodríguez, Á., et al. (2020) · Aging Cell · doi:10.1111/acel.13183 · Cited by 33
“Precisely, induction of senescence by p53 activation in malignant hepatocytes showed a reduction in the tumor size caused by SASP‐mediated recruitment of immune cells to the tumors (Lujambio et al., 2013).”
Molecular dynamics of the full-length p53 monomer
Chillemi, G., Davidovich, P. B., D’Abramo, M., Mametnabiev, T. E., Garabadzhiu, A. V., Desideri, A., & Melino, G. (2013) · Cell Cycle · doi:10.4161/cc.26162 · Cited by 31
Ligand dependent restoration of human TLR3 signaling and death in p53 mutant cells
Menendez, D., Lowe, J. M., Snipe, J., & Resnick, M. A. (2016) · Oncotarget · doi:10.18632/oncotarget.11210 · Cited by 31
“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].”
BackgroundA nutrigeroscience approach: Dietary macronutrients and cellular senescence
Calubag, M. F., Robbins, P. D., & Lamming, D. W. (2024) · Cell Metabolism · doi:10.1016/j.cmet.2024.07.025 · Cited by 33
Hepatic stellate cell heterogeneity: Functional aspects and therapeutic implications
Geng, Y., & Schwabe, R. F. (2025) · Hepatology · doi:10.1097/hep.0000000000001386 · Cited by 34
P53 Mutant p53N236S Regulates Cancer-Associated Fibroblasts Properties Through Stat3 Pathway
Liu, Q., Yu, B., Tian, Y., Dan, J., Luo, Y., & Wu, X. (2020) · OncoTargets and Therapy · doi:10.2147/ott.s229065 · Cited by 31
“in a cell non-cell-autonomous manner, thereby promoting an anti-tumorigenic microenvironment.(10) p53 is mutated in more than 50% of human cancers.”
BackgroundEmergency myelopoiesis in solid cancers
Aliazis, K., Yenyuwadee, S., Phikulsod, P., & Boussiotis, V. A. (2024) · British Journal of Haematology · doi:10.1111/bjh.19656 · Cited by 34
“54 Similarly, the cyclic GMP-AMP synthase which activates the stimulator of interferon genes (cGAS-STING) pathway can detect cytosolic DNA and induce SASP through secretion of pro-inflammatory cytokines such as IL-1, IL-6, and IL-8, leading to increased immuno-surveillance and clearance of the…”
The Role of Nitric Oxide from Neurological Disease to Cancer
Maher, A., Rahman, M. F. A., & Gad, M. Z. (2017) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-60733-7_5 · Cited by 30
“p53 eliminates tumor cells through the induction of senescence mediated by the cell cycle inhibitor p21 leading to tumor cells engulfment by macrophages [72].”
BackgroundXia, Y., Du, Z., Wang, X., & Li, X. (2017) · Human Gene Therapy · doi:10.1089/hum.2017.206 · Cited by 32
“72 p53 also directly regulates NK cell transcription, enhancing the ability of these cells to kill tumor cells, and activates the antitumor immune response.”
Aging Kidney and Aging-Related Disease
Li, Z., & Wang, Z. (2018) · Advances in experimental medicine and biology · doi:10.1007/978-981-13-1117-8_11 · Cited by 29
Fasoulakis, Z. N., Daskalakis, G. J., Diakosavvas, M., Papapanagiotou, I., Theodora, M. K., Bourazan, A., Alatzidou, D., Pagkalos, A., & Kontomanolis, E. N. (2019) · MicroRNA · doi:10.2174/2211536608666190919161849 · Cited by 39
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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