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Inside and out: the activities of senescence in cancer
Open accessAbstract
The core aspect of the senescent phenotype is a stable state of cell cycle arrest. However, this is a disguise that conceals a highly active metabolic cell state with diverse functionality. Both the cell-autonomous and the non-cell-autonomous activities of senescent cells create spatiotemporally dynamic and context-dependent tissue reactions. For example, the senescence-associated secretory phenotype (SASP) provokes not only tumour-suppressive but also tumour-promoting responses. Senescence is now increasingly considered to be an integrated and widespread component that is potentially important for tumour development, tumour suppression and the response to therapy.
Overview
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Written from the paper’s full text.
TL;DR
This review argues that senescence is more than a stable proliferative arrest: senescent cells remain metabolically active and communicate with their surroundings through secreted factors. It surveys how these cell-intrinsic and cell-extrinsic activities can suppress or promote cancer depending on context, with implications for therapy.
Key findings
- Senescence is heterogeneous and usually involves p53 and RB pathways, alongside telomere shortening/DNA damage responses, autophagy, metabolic shifts, altered secretion, and epigenetic regulation; multiple markers are needed for confident identification.
- In oncogene-induced and therapy-induced senescence, mitochondrial oxidative phosphorylation can be hyperactive. PDH activity rises in BRAF-V600E- or RAS-G12V-driven senescence; reducing PDH blocks BRAF-V600E senescence, while activating PDH is sufficient to induce senescence in normal cells. In human melanoma, roughly 10% of tumours had above-average PGC1α expression, and MITF/PGC1α-expressing melanoma cells were more resistant to oxidative stress and associated with poor prognosis.
- Autophagy is activated during senescence and can support SASP components such as IL-6 and IL-8, but its role varies by context; blocking autophagy can delay senescence, cause cell death, or exacerbate senescence depending on the model.
- The SASP can reinforce or spread senescence, recruit innate and adaptive immune cells to clear senescent cells, or promote tumorigenesis. Examples include NK-cell-mediated clearance via NKG2D–RAE1 and CD4+ T-cell-dependent senescence surveillance; stromal senescence can limit fibrosis and hepatocellular carcinoma in some models but promote hepatocellular carcinoma in an obesity/deoxycholic acid model.
Methods
- Narrative review; no primary experimental design, dataset, or statistical analysis is reported.
- The paper synthesizes published in vitro, mouse-model, and human tumour studies across pre-neoplasia, therapy-induced senescence, metabolism, autophagy, SASP, immune clearance, stromal senescence, and cytokine-mediated senescence.
- Data or sample: Not stated in the paper (no new data collected).
Limitations
- The paper states that many mechanisms remain unclear and context-dependent, including why mitochondrial dysfunction versus hyperactive respiration is observed, why stromal SASP effects differ between models, and how autophagy acts differently across tissues; further study is needed.
- Evident from the text: as a review, it does not describe a systematic search or quantitative synthesis, and its conclusions depend on heterogeneous models and contexts.
- Evident from the text: several sections contain editorial queries and incomplete figure/table formatting, which limits clarity but does not alter the scientific claims summarized.
Model-written summary. Check it against the paper before relying on it.
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Claims the paper makes
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In the paper
“senescent cells can exhibit hyperactive mitochondrial respiration (oxidative phosphorylation ) in some contexts.”
§ Inside and out; the activities of senescence in cancer > Abstract
What the sources say
- Not checked yetcites [41] Kaplon, J. et al. A key role for mitochondrial gatekeeper pyruvate dehydrogenase in oncogene-induced senescence. Nature 498, 109–112 (2013). This study established the metabolic profile of OIS cells, identifying active PDH with increased mitochondrial respiration during OIS. source
- Not checked yetcites [42] Kondoh, H. et al. Glycolytic enzymes can modulate cellular life span. Cancer Res. 65, 177–185 (2005). source
- Not checked yetcites [43] Dörr, J. R. et al. Synthetic lethal metabolic targeting of cellular senescence in cancer therapy. Nature 501, 421–425 (2013). This study shows that in a TIS model, the SASP, which provokes endoplasmic reticulum stress, is associated with increased glucose use, hyperactive mitochondrial respiration, and autophagy activation, and that TIS cells are sensitive to blocking glucose use or autophagy, which causes endoplasmic reticulum-related apoptosis. source
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“In contrast to tumour cells, which typically preferentially use glycolysis in the presence of oxygen to generate energy”
§ Inside and out; the activities of senescence in cancer > Abstract
What the sources say
- Not checked yetcites [40] Koppenol, W. H., Bounds, P. L. & Dang, C. V. Otto Warburg's contributions to current concepts of cancer metabolism. Nature Rev. Cancer 11, 325–337 (2011). source
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In the paper
“Senescent cells are metabolically active.”
§ Inside and out; the activities of senescence in cancer > Abstract
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In the paper
“recent studies have identified two distinct sub-groups in human melanoma: a conventional glycolytic group and a group characterised by high rates of oxidative phosphorylation 47,48 .”
§ Inside and out; the activities of senescence in cancer > Mitochondrial metabolism
What the sources say
- Not checked yetcites [47] Haq, R. et al. Oncogenic BRAF regulates oxidative metabolism via PGC1α and MITF. Cancer Cell 23, 302–315 (2013). source
- Not checked yetcites [48] Vazquez, F. et al. PGC1α expression defines a subset of human melanoma tumors with increased mitochondrial capacity and resistance to oxidative stress. Cancer Cell 23, 287–301 (2013). source
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In the paper
“a series of studies [22][23][24][25][26] identified senescence in several premalignant tumours, both in humans and mice.”
§ Inside and out; the activities of senescence in cancer > Senescence in pre-neoplasia
What the sources say
- Not checked yetcites [22] Braig, M. et al. Oncogene-induced senescence as an initial barrier in lymphoma development. Nature 436, 660–665 (2005). source
- Not checked yetcites [23] Chen, Z. et al. Crucial role of p53-dependent cellular senescence in suppression of Pten-deficient tumorigenesis. Nature 436, 725–730 (2005). source
- Not checked yetcites [24] Collado, M. et al. Tumour biology: Senescence in premalignant tumours. Nature 436, 642–642 (2005). source
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In the paper
“Senescent cells can be eliminated through a SASP-induced immune response, which can involve both innate and adaptive immunity.”
§ Inside and out; the activities of senescence in cancer > Abstract
What the sources say
- Not checked yetcites [111] Hoenicke, L. & Zender, L. Immune surveillance of senescent cells—biological significance in cancer- and non-cancer pathologies. Carcinogenesis 33, 1123–1126 (2012). source
- Not checked yetcites [112] Kang, T.-W. et al. Senescence surveillance of pre-malignant hepatocytes limits liver cancer development. Nature 479, 547–551 (2011). This is a seminal study that identifies senescence surveillance involving the adaptive immune response. source
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In the paper
“Loss of telomerase activity in mice has been shown to suppress tumorigenesis in various tumour models [13][14][15][16]”
§ Inside and out; the activities of senescence in cancer > Senescence in pre-neoplasia
What the sources say
- Not checked yetcites [13] González-Suárez, E., Samper, E., Flores, J. M. & Blasco, M. A. Telomerase-deficient mice with short telomeres are resistant to skin tumorigenesis. Nature Genet. 26, 114–117 (2000). source
- Not checked yetcites [14] Greenberg, R. A. et al. Short dysfunctional telomeres impair tumorigenesis in the INK4a(delta2/3) cancer-prone mouse. Cell 97, 515–525 (1999). source
- Not checked yetcites [15] Qi, L. et al. Short telomeres and ataxia-telangiectasia mutated deficiency cooperatively increase telomere dysfunction and suppress tumorigenesis. Cancer Res. 63, 8188–8196 (2003).
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesThe paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Senescence can also be induced in response to therapy-induced genotoxic stress.”
§ Inside and out; the activities of senescence in cancer > Therapy-induced senescence
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesThe paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Various triggers such as tissue damage or tumorigenesis-associated stresses can cause stromal cell senescence”
§ Inside and out; the activities of senescence in cancer > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes? Based: unclearIn the paper
“telomere attrition-induced senescence is implicated in these tumour suppressive effects 17 .”
§ Inside and out; the activities of senescence in cancer > Senescence in pre-neoplasia
What the sources say
- Not checked yetcites [17] Feldser, D. M. & Greider, C. W. Short telomeres limit tumor progression in vivo by inducing senescence. Cancer Cell 11, 461–469 (2007). source
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- Probably not a substantial claim. 8
- It may state two separate claims as one. 37
- The quote only partly states this claim. 3
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Induction of senescence, a stable state of cell cycle arrest, was originally described in normal cells, but it can also be induced in tumour cells in response to various stresses.”
§ Inside and out; the activities of senescence in cancer > Abstract
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The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“the long-term fate of senescent cells, which, similar to apoptotic cells, can be cleared from lesions in some contexts.”
§ Inside and out; the activities of senescence in cancer > Introduction
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In the paper
“However, the prognosis of these mice was significantly better than the Eµ-Myc; Trp53 -/-mice because the cells in the Eµ-Myc; Bcl2 lymphomas became senescent, although the Eµ-Myc; Bcl2 lymphomas also eventually progressed.”
§ Inside and out; the activities of senescence in cancer > Therapy-induced senescence
What the sources say
- Not checked yetcites [32] Schmitt, C. A. et al. A senescence program controlled by p53 and p16INK4a contributes to the outcome of cancer therapy. Cell 109, 335–346 (2002). This was the first study showing that chemotherapy-induced tumour senescence contributed to improved survival in mice, in an apoptosis defective context. source
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In the paper
“Quijano et al. 53 showed that HRAS-G12V-induced senescent HDFs exhibit reduced lipid synthesis and increased fatty acid (FA) oxidation, leading to enhanced mitochondrial oxygen consumption.”
§ Inside and out; the activities of senescence in cancer > Mitochondrial metabolism
What the sources say
- Not checked yetcites [53] Quijano, C. et al. Oncogene-induced senescence results in marked metabolic and bioenergetic alterations. Cell Cycle 11, 1383–1392 (2012). source
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The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Senescence has a heterogeneous phenotype in terms of cellular markers: multiple markers are required to define senescence with confidence.”
§ Inside and out; the activities of senescence in cancer > Introduction
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In the paper
“These include telomere shortening and a persistent DNA damage response, autophagy and other metabolic alterations, altered protein secretion, and epigenetic gene regulation [2][3][4] .”
§ Inside and out; the activities of senescence in cancer > Introduction
What the sources say
- Not checked yetcites [2] D'adda Di Fagagna, F. Living on a break: cellular senescence as a DNA-damage response. Nature Rev. Cancer 8, 512–522 (2008). source
- Not checked yetcites [3] Kuilman, T., Michaloglou, C., Mooi, W. J. & Peeper, D. S. The essence of senescence. Genes Dev. 24, 2463–2479 (2010). source
- Not checked yetcites [4] Salama, R., Sadaie, M., Hoare, M. & Narita, M. Cellular senescence and its effector programs. Genes Dev. 28, 99–114 (2014). source
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In the paper
“including reinforcing or inducing senescence”
§ Inside and out; the activities of senescence in cancer > Abstract
What the sources say
- Not checked yetcites [91] Kuilman, T. et al. Oncogene-induced senescence relayed by an interleukin-dependent inflammatory network. Cell 133, 1019–1031 (2008). source
- Not checked yetcites [92] Acosta, J. C. et al. Chemokine signaling via the CXCR2 receptor reinforces senescence. Cell 133, 1006–1018 (2008). References 91 and 92 describe the crucial role of pro-inflammatory cytokines and their receptors in senescence. source
- Not checked yetcites [105] Coppé, J.-P. et al. Senescence-associated secretory phenotypes reveal cell-nonautonomous functions of oncogenic RAS and the p53 tumor suppressor. Plos Biol. 6, 2853–2868 (2008). source
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In the paper
“ME1 and ME2 expression is repressed by p53 and the MEs negatively regulate p53, thus depletion of the MEs results in p53 activation in a feed forward manner, thereby inducing senescence 50 (FIG.1).”
§ Inside and out; the activities of senescence in cancer > Mitochondrial metabolism
What the sources say
- Not checked yetcites [50] Jiang, P., Du, W., Mancuso, A., Wellen, K. E. & Yang, X. Reciprocal regulation of p53 and malic enzymes modulates metabolism and senescence. Nature 493, 689–693 (2013). This study shows that malic enzymes and p53 reciprocally repress each other and that depletion of ME1 or ME2 induces senescence in both normal and tumour cells. source
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In the paper
“Autophagy is dynamically activated during OIS and facilitates the synthesis of interleukin 6 (IL-6) and IL-8, major components of the SASP 58,59 .”
§ Inside and out; the activities of senescence in cancer > Autophagy
What the sources say
- Not checked yetcites [58] Narita, M. et al. Spatial coupling of mTOR and autophagy augments secretory phenotypes. Science 332, 966–970 (2011). source
- Not checked yetcites [59] Young, A. R. J. et al. Autophagy mediates the mitotic senescence transition. Genes Dev. 23, 798–803 (2009). This study shows that autophagy is activated during senescence and that the inhibition of autophagy delays the onset of senescence and the SASP. source
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In the paper
“activation of PDH in mutant BRAF-driven human melanoma cells not only blocks tumorigenesis but also sensitises them to the BRAF inhibitor PLX4720 (an analogue of vemurafenib), eliminating treatment-resistant cell populations 41 .”
§ Inside and out; the activities of senescence in cancer > Mitochondrial metabolism
What the sources say
- Not checked yetcites [41] Kaplon, J. et al. A key role for mitochondrial gatekeeper pyruvate dehydrogenase in oncogene-induced senescence. Nature 498, 109–112 (2013). This study established the metabolic profile of OIS cells, identifying active PDH with increased mitochondrial respiration during OIS. source
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The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Senescence typically depends on the p53 and RB pathways, but other effector programs confer additional layers of regulation.”
§ Inside and out; the activities of senescence in cancer > Introduction
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In the paper
“In this model, autophagy deficient mice exhibit a marked but transient accumulation of early PanIN accompanied by increased rates of apoptotic cell death, and these lesions never progress to late stage PanINs or PDA 87 .”
§ Inside and out; the activities of senescence in cancer > Autophagy
What the sources say
- Not checked yetcites [87] Rosenfeldt, M. T. et al. p53 status determines the role of autophagy in pancreatic tumour development. Nature 504, 296–300 (2014). source
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In the paper
“some SASP components not only reinforce the senescence response in cells that are already primed for senescence, but also induce senescence in normal neighbouring cells in a paracrine fashion 93,106”
§ Inside and out; the activities of senescence in cancer > Cytokine-mediated senescence
What the sources say
- Not checked yetcites [93] Acosta, J. C. et al. A complex secretory program orchestrated by the inflammasome controls paracrine senescence. Nature Cell Biol. 15, 978–990 (2013). This study identified the inflammasome as a critical regulator of the SASP. source
- Not checked yetcites [106] Hubackova, S. et al. IL1- and TGFβ-Nox4 signaling, oxidative stress and DNA damage response are shared features of replicative, oncogene-induced, and drug-induced paracrine 'bystander senescence'. Aging 4, 932–951 (2012). source
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In the paper
“In an Eµ-Myc lymphoma model, p53induced apoptosis of lymphoma cells led to the activation of macrophages to secrete TGFß1, which in turn induced senescence in lymphoma cells 36”
§ Inside and out; the activities of senescence in cancer > Cytokine-mediated senescence
What the sources say
- Not checked yetcites [36] Reimann, M. et al. Tumor stroma-derived TGF-b limits Myc-Driven lymphomagenesisvia Suv39h1-dependent senescence. Cancer Cell 17, 262–272 (2010). source
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These data indicate that senescence in the context of some forms of tissue damage involves the spatio-temporal control of secreted protein levels as well as the content of SASP, which in turn modulates the senescence phenotype and dynamically regulates the surrounding tissue integrity; eventually contributing to the resolution of the lesion.”
§ Inside and out; the activities of senescence in cancer > Senescence in the stroma
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In the paper
“Treatment of mice with Tag-T H 1 cells in this model induces a cell proliferation arrest in the tumors and improves the survival of these mice 128”
§ Inside and out; the activities of senescence in cancer > Cytokine-mediated senescence
What the sources say
- Not checked yetcites [128] Müller-Hermelink, N. et al. TNFR1 signaling and IFN-γ signaling determine whether T cells induce tumor dormancy or promote multistage carcinogenesis. Cancer Cell 13, 507–518 (2008). source
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In the paper
“pancreatic acinar cells, in which Kras-G12V is activated during adulthood, exhibit a low frequency of PanIN development and resistance to transformation, at least in part due to OIS 118”
§ Inside and out; the activities of senescence in cancer > Clearance of senescent cells through an immune response
What the sources say
- Not checked yetcites [118] Guerra, C. et al. Pancreatitis-induced inflammation contributes to pancreatic cancer by inhibiting oncogene-induced senescence. Cancer Cell 19, 728–739 (2011). source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“activated HSCs become senescent, exhibiting a typical SASP, including the expression of extracellular matrix degrading enzymes and proinflammatory cytokines.”
§ Inside and out; the activities of senescence in cancer > Senescence in the stroma
What the sources say
- Not checked yetcites [94] Lujambio, A. et al. Non-cell-autonomous tumor suppression by p53. Cell 153, 449–460 (2013). source
- Not checked yetcites [120] Krizhanovsky, V. et al. Senescence of activated stellate cells limits liver fibrosis. Cell 134, 657–667 (2008). This was the first study to show that HSC senescence controls fibrosis through the SASP. source
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In the paper
“Although Tag binds both RB and p53, it attenuates, rather than fully inactivates, their activity, thus their residual activities allow the RIP-Tag2 mice to exhibit progressive tumorigenesis with only a small portion of islets developing invasive pancreatic cancer 127,129”
§ Inside and out; the activities of senescence in cancer > Cytokine-mediated senescence
What the sources say
- Not checked yetcites [127] Bergers, G., Javaherian, K., Lo, K. M., Folkman, J. & Hanahan, D. Effects of angiogenesis inhibitors on multistage carcinogenesis in mice. Science 284, 808–812 (1999). source
- Not checked yetcites [129] Casanovas, O., Hager, J. H., Chun, M. G. H. & Hanahan, D. Incomplete inhibition of the Rb tumor suppressor pathway in the context of inactivated p53 is sufficient for pancreatic islet tumorigenesis. Oncogene 24, 6597–6604 (2005). source
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In the paper
“in contrast to the pancreas model, autophagy deficiency (by autophagy related 7 (Atg7) knockout) suppresses Kras G12D -driven lung cancer development even in the absence of Trp53; presumably this is partially due to mitochondrial dysfunction.”
§ Inside and out; the activities of senescence in cancer > Autophagy
What the sources say
- Not checked yetcites [88] Guo, J. Y. et al. Autophagy suppresses progression of K-ras-induced lung tumors to oncocytomas and maintains lipid homeostasis. Genes Dev. 27, 1447–1461 (2013). source
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In the paper
“CCN1 can also promote myofibroblast senescence, which is associated with the expression of antifibrotic genes in the skin, thus CCN1 mediated stromal senescence might be involved in wound healing 123”
§ Inside and out; the activities of senescence in cancer > Senescence in the stroma
What the sources say
- Not checked yetcites [123] Jun, J.-I. & Lau, L. F. The matricellular protein CCN1 induces fibroblast senescence and restricts fibrosis in cutaneous wound healing. Nature Cell Biol. 12, 676–685 (2010). source
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“The senescence phenotype is dependent on the p16-RB pathway, thus unlike the aforementioned Tag-driven hepatoma model, the residual RB activity seems to be sufficient for senescence induction in this model 129”
§ Inside and out; the activities of senescence in cancer > Cytokine-mediated senescence
What the sources say
- Not checked yetcites [129] Casanovas, O., Hager, J. H., Chun, M. G. H. & Hanahan, D. Incomplete inhibition of the Rb tumor suppressor pathway in the context of inactivated p53 is sufficient for pancreatic islet tumorigenesis. Oncogene 24, 6597–6604 (2005). source
Strength:hedged· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“human melanocytic naevi (an OIS model), remain non-proliferative for decades without transformation into malignant melanoma 25”
§ Inside and out; the activities of senescence in cancer > Clearance of senescent cells through an immune response
What the sources say
- Not checked yetcites [25] Michaloglou, C. et al. BRAFE600-associated senescence-like cell cycle arrest of human naevi. Nature 436, 720–724 (2005). This is a seminal study that identified OIS of human melanocytic naevi. source
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None of the sources cited for this claim have been checked yet.
In the paper
“these same factors can facilitate senescence in a cell-autonomous fashion, thus amplifying the phenotype 91,92,105”
§ Inside and out; the activities of senescence in cancer > Senescence-associated secretory phenotype (SASP)
What the sources say
- Not checked yetcites [91] Kuilman, T. et al. Oncogene-induced senescence relayed by an interleukin-dependent inflammatory network. Cell 133, 1019–1031 (2008). source
- Not checked yetcites [92] Acosta, J. C. et al. Chemokine signaling via the CXCR2 receptor reinforces senescence. Cell 133, 1006–1018 (2008). References 91 and 92 describe the crucial role of pro-inflammatory cytokines and their receptors in senescence. source
- Not checked yetcites [105] Coppé, J.-P. et al. Senescence-associated secretory phenotypes reveal cell-nonautonomous functions of oncogenic RAS and the p53 tumor suppressor. Plos Biol. 6, 2853–2868 (2008). source
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In the paper
“Re-expression of endogenous p53 induced senescence and the elimination of the senescent tumour cells was mediated by innate immune cells, including macrophages, neutrophils and natural killer (NK) cells, albeit in mice lacking an adaptive immune system.”
§ Inside and out; the activities of senescence in cancer > Clearance of senescent cells through an immune response
What the sources say
- Not checked yetcites [34] Xue, W. et al. Senescence and tumour clearance is triggered by p53 restoration in murine liver carcinomas. Nature 445, 656–660 (2007). This was the first study to show that the innate immune response eliminates the senescent cells induced in tumours in mice. source
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In the paper
“episodic pancreatitis induced by caerulein, a decapeptide analog of the gastrointestinal peptide hormone cholecystokinin, inhibited the OIS program, thus facilitating malignant transformation in this model 118”
§ Inside and out; the activities of senescence in cancer > Clearance of senescent cells through an immune response
What the sources say
- Not checked yetcites [118] Guerra, C. et al. Pancreatitis-induced inflammation contributes to pancreatic cancer by inhibiting oncogene-induced senescence. Cancer Cell 19, 728–739 (2011). source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“the depletion of MYC in a mouse subcutaneous transplantation model of T cell acute lymphoblastic lymphoma (T-ALL), which carries tetracycline regulated MYC transgene, results in sustained tumour regression associated with senescence and apoptosis, where an adaptive immune response (involving CD4 + T cells in particular) was required for senescence induction and sustained tumour regression, but not”
§ Inside and out; the activities of senescence in cancer > Clearance of senescent cells through an immune response
What the sources say
- Not checked yetcites [116] Rakhra, K. et al. CD4(+) T cells contribute to the remodeling of the microenvironment required for sustained tumor regression upon oncogene inactivation. Cancer Cell 18, 485–498 (2010). source
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In the paper
“The SASP also attracts innate immune cells that in turn eliminate the senescent HSCs and facilitate the resolution of fibrosis 94,120”
§ Inside and out; the activities of senescence in cancer > Senescence in the stroma
What the sources say
- Not checked yetcites [94] Lujambio, A. et al. Non-cell-autonomous tumor suppression by p53. Cell 153, 449–460 (2013). source
- Not checked yetcites [120] Krizhanovsky, V. et al. Senescence of activated stellate cells limits liver fibrosis. Cell 134, 657–667 (2008). This was the first study to show that HSC senescence controls fibrosis through the SASP. source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“The TAA-expressing islets treated with Tag-T H 1 cells are functional (i.e. they produce insulin), thus appeared to be in a state of tumour dormancy 128”
§ Inside and out; the activities of senescence in cancer > Cytokine-mediated senescence
What the sources say
- Not checked yetcites [128] Müller-Hermelink, N. et al. TNFR1 signaling and IFN-γ signaling determine whether T cells induce tumor dormancy or promote multistage carcinogenesis. Cancer Cell 13, 507–518 (2008). source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“| | LSL-Kras G12V ; RERTn +/ERT | Cdk4 ablation | development | 158 | | | |”
- Also stated in: § Additional information · plain
“| | | | | | Suppression of non-small cell lung carcinoma | | |”
§ Inside and out; the activities of senescence in cancer > Additional information
What the sources say
- Not checked yetcites [158] Puyol, M. et al. A synthetic lethal interaction between K-Ras oncogenes and Cdk4 unveils a therapeutic strategy for non-small cell lung carcinoma. Cancer Cell 18, 63–73 (2010). source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesThe quote only partly states this claim.
- Also stated in: § Additional information · plain
In the paper
“This is a seminal study that identified OIS of human melanocytic naevi.”
§ Inside and out; the activities of senescence in cancer > References
What the sources say
- Not checked yetcites [25] Michaloglou, C. et al. BRAFE600-associated senescence-like cell cycle arrest of human naevi. Nature 436, 720–724 (2005). This is a seminal study that identified OIS of human melanocytic naevi. source
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“This seminal paper established the concept of OIS.”
§ Inside and out; the activities of senescence in cancer > References
What the sources say
- Not checked yetcites [19] Serrano, M., Lin, A. W., McCurrach, M. E., Beach, D. & Lowe, S. W. Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a. Cell 88, 593–602 (1997). This seminal paper established the concept of OIS. source
Strength:boosted· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“Embryonic cell senescence is p21, but not p53, dependent, is accompanied by the SASP, and these cells are eliminated by macrophages 149,150”
§ Inside and out; the activities of senescence in cancer > Embryogenesis:
What the sources say
- Not checked yetcites [149] Muñoz-Espín, D. et al. Programmed cell senescence during mammalian embryonic development. Cell 155, 1104–1118 (2013). source
- Not checked yetcites [150] Storer, M. et al. Senescence is a developmental mechanism that contributes to embryonic growth and patterning. Cell 155, 1119–1130 (2013). source
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In the paper
“| CDK4 inhibitor | LSL-Kras G12V ; RERTn +/ERT | PD0332991 | development | 158 | | | |”
- Also stated in: § Additional information · plain
“| | | | | | Suppression of non-small cell lung carcinoma | | |”
§ Inside and out; the activities of senescence in cancer > Additional information
What the sources say
- Not checked yetcites [158] Puyol, M. et al. A synthetic lethal interaction between K-Ras oncogenes and Cdk4 unveils a therapeutic strategy for non-small cell lung carcinoma. Cancer Cell 18, 63–73 (2010). source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesThe quote only partly states this claim.
- Also stated in: § Additional information · plain
None of the sources cited for this claim have been checked yet.
In the paper
“The partial induction of senescence in tumours could eradicate or exacerbate the tumours 110,113”
§ Inside and out; the activities of senescence in cancer > Concluding remarks
What the sources say
- Not checked yetcites [110] Jackson, J. G. et al. p53-mediated senescence impairs the apoptotic response to chemotherapy and clinical outcome in breast cancer. Cancer Cell 21, 793–806 (2012). source
- Not checked yetcites [113] Iannello, A., Thompson, T. W., Ardolino, M., Lowe, S. W. & Raulet, D. H. p53-dependent chemokine production by senescent tumor cells supports NKG2D-dependent tumor elimination by natural killer cells. J. Exp. Med. 210, 2057–2069 (2013). This study suggests that NK cells that are recruited to the tumour lesion by the SASP of senescent tumour cells may also kill non-senescent tumour cells. source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“This study established the metabolomics profile of OIS cells, identifying active PDH with increased mitochondrial respiration during OIS.”
§ Inside and out; the activities of senescence in cancer > References
What the sources say
- Not checked yetcites [41] Kaplon, J. et al. A key role for mitochondrial gatekeeper pyruvate dehydrogenase in oncogene-induced senescence. Nature 498, 109–112 (2013). This study established the metabolic profile of OIS cells, identifying active PDH with increased mitochondrial respiration during OIS. source
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“age-dependent accumulation of p16-positive cells in tissue stem cell or progenitor cell compartments contributes to tissue degeneration, and p16 depletion attenuates some age-dependent phenotypes [145][146][147]”
§ Inside and out; the activities of senescence in cancer > Box 1: Consequences of cellular senescence: aging and development
What the sources say
- Not checked yetcites [145][146][147]
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“Much like dormant cells, senescent cells are resistant to apoptosis or mitotic catastrophe upon chemotherapy, thus if senescent tumour cells are not eliminated, the sustained expression of pro-tumorigenic cytokines can lead to a worse outcome 110”
§ Inside and out; the activities of senescence in cancer > Concluding remarks
What the sources say
- Not checked yetcites [110] Jackson, J. G. et al. p53-mediated senescence impairs the apoptotic response to chemotherapy and clinical outcome in breast cancer. Cancer Cell 21, 793–806 (2012). source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“| SKP2 inhibitor | xenografts | | | SKP2 Inhibitor#25 | Tumour growth inhibition | 159 |”
- Also stated in: § Additional information · plain
“| | Human lung and prostate cancer | | | | | | |”
§ Inside and out; the activities of senescence in cancer > Additional information
What the sources say
- Not checked yetcites [159] Chan, C.-H. et al. Pharmacological inactivation of Skp2 SCF ubiquitin ligase restricts cancer stem cell traits and cancer progression. Cell 154, 556–568 (2013). source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesThe quote only partly states this claim.
- Also stated in: § Additional information · plain
None of the sources cited for this claim have been checked yet.
In the paper
“the majority of prostate cancer patients at presentation have lost one allele of PTEN while maintaining intact TP53; whereas TP53 mutations and the complete loss of PTEN are both associated with advanced stage prostate cancer 153,154”
§ Inside and out; the activities of senescence in cancer > Box 2: PTEN loss-induced cellular senescence (PICS)
What the sources say
- Not checked yetcites [153] Schlomm, T. et al. Clinical significance of p53 alterations in surgically treated prostate cancers. Mod. Pathol. 21, 1371–1378 (2008). source
- Not checked yetcites [154] Song, M. S., Salmena, L. & Pandolfi, P. P. The functions and regulation of the PTEN tumour suppressor. Nature Rev. Mol. Cell. Biol. 13, 283–296 (2012). source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“Pten heterozygosity promotes tumour initiation and proliferation in the prostate, but paradoxically, the complete loss of Pten can oppose prostate tumorigenesis by triggering a powerful p53-dependent cellular senescence response 38”
§ Inside and out; the activities of senescence in cancer > Box 2: PTEN loss-induced cellular senescence (PICS)
What the sources say
- Not checked yetcites [38] Nardella, C., Clohessy, J. G., Alimonti, A. & Pandolfi, P. P. Pro-senescence therapy for cancer treatment. Nature Rev. Cancer 11, 503–511 (2011). source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“| | haematopoietic system | MYC suppression | lymphoma | 116 | | | |”
§ Inside and out; the activities of senescence in cancer > Additional information
What the sources say
- Not checked yetcites [116] Rakhra, K. et al. CD4(+) T cells contribute to the remodeling of the microenvironment required for sustained tumor regression upon oncogene inactivation. Cancer Cell 18, 485–498 (2010). source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✗ Asserted: fails✓ Checkable: passes✗ Load-bearing: fails✗ Based: failsProbably not a substantial claim. The authors may not put it forward as true. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“unlike p16-ablation, elimination of p16-expressing cells does not facilitate tumorigenesis in this model.”
§ Inside and out; the activities of senescence in cancer > Box 1: Consequences of cellular senescence: aging and development
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“This study suggests that NK cells recruited to the tumour lesion by the SASP of senescent tumour cells may also kill non-senescent tumour cells.”
§ Inside and out; the activities of senescence in cancer > References
What the sources say
- Not checked yetcites [113] Iannello, A., Thompson, T. W., Ardolino, M., Lowe, S. W. & Raulet, D. H. p53-dependent chemokine production by senescent tumor cells supports NKG2D-dependent tumor elimination by natural killer cells. J. Exp. Med. 210, 2057–2069 (2013). This study suggests that NK cells that are recruited to the tumour lesion by the SASP of senescent tumour cells may also kill non-senescent tumour cells. source
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“This study shows that in a TIS model the SASP, which provokes endoplasmic reticulum (ER) stress, is associated with increased glucose use, hyperactive mitochondrial respiration, and autophagy activation”
§ Inside and out; the activities of senescence in cancer > References
What the sources say
- Not checked yetcites [43] Dörr, J. R. et al. Synthetic lethal metabolic targeting of cellular senescence in cancer therapy. Nature 501, 421–425 (2013). This study shows that in a TIS model, the SASP, which provokes endoplasmic reticulum stress, is associated with increased glucose use, hyperactive mitochondrial respiration, and autophagy activation, and that TIS cells are sensitive to blocking glucose use or autophagy, which causes endoplasmic reticulum-related apoptosis. source
Strength:boosted· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“This study shows that Malic enzymes (MEs) and p53 reciprocally repress each other”
§ Inside and out; the activities of senescence in cancer > References
What the sources say
- Not checked yetcites [50] Jiang, P., Du, W., Mancuso, A., Wellen, K. E. & Yang, X. Reciprocal regulation of p53 and malic enzymes modulates metabolism and senescence. Nature 493, 689–693 (2013). This study shows that malic enzymes and p53 reciprocally repress each other and that depletion of ME1 or ME2 induces senescence in both normal and tumour cells. source
Strength:boosted· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“In fact, senescent cells secrete an array of inflammatory proteins, growth factors, and metalloproteases that collectively constitute the SASP (senescence-associated secretory phenotype).”
From Integrin Beta 3 Regulates Cellular Senescence by Activating the TGF-β Pathway (2017) · cites this paper as Pérez-Mancera et al., 2014
In the citing paper
“However, the deleterious consequences that result from ineffective clearance of senescent cells and their over-accumulation in tissues can promote age-related diseases and cancer.2,26–30”
From Paracrine roles of cellular senescence in promoting tumourigenesis (2018) · cites this paper as [30]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Lung cancer model has two different KRAS mutations
MinorThe same discussion identifies the autophagy-inhibition lung model as KRAS-G12V-driven and then as KRAS-G12D-driven. These are different mutations, so the model is described inconsistently.
“Interestingly, the effect of autophagy inhibition in Kras G12V -driven lung tumorigenesis (another OIS model 24 ) is distinct from the pancreas model.”
“Thus, in contrast to the pancreas model, autophagy deficiency (by autophagy related 7 (Atg7) knockout) suppresses Kras G12D -driven lung cancer development even in the absence of Trp53; presumably this is partially due to mitochondrial dysfunction.”
Citations
Cites
1 retracted
Mariño, G., Salvador-Montoliu, N., Fueyo, A., Knecht, E., Mizushima, N., & López-Otı́n, C. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m701194200 · Cited by 427
RetractedLópez-Otín, C., Blasco, M. A., Partridge, L., Serrano, M., & Kroemer, G. (2013) · Cell · doi:10.1016/j.cell.2013.05.039 · Cited by 14,982
The serial cultivation of human diploid cell strains
Hayflick, L., & Moorhead, P. S. (1961) · Experimental Cell Research · doi:10.1016/0014-4827(61)90192-6 · Cited by 8,508
Autophagy: Renovation of Cells and Tissues
Mizushima, N., & Komatsu, M. (2011) · Cell · doi:10.1016/j.cell.2011.10.026 · Cited by 6,615
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
Telomeres shorten during ageing of human fibroblasts
Harley, C. B., Futcher, A. B., & Greider, C. W. (1990) · Nature · doi:10.1038/345458a0 · Cited by 5,750
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
The senescence-associated secretory phenotype: the dark side of tumor suppression
Coppé, J.-P., Desprez, P.-Y., Krtolica, A., & Campisi, J. (2010) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev-pathol-121808-102144 · Cited by 5,206
Cellular senescence: when bad things happen to good cells
Campisi, J., & d'Adda di Fagagna, F. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2233 · Cited by 4,441
Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders
Baker, D. J., Wijshake, T., Tchkonia, T., LeBrasseur, N. K., Childs, B. G., van de Sluis, B., Kirkland, J. L., & van Deursen, J. M. (2011) · Nature · doi:10.1038/nature10600 · Cited by 3,670
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Senescence in Health and Disease
He, S., & Sharpless, N. E. (2017) · Cell · doi:10.1016/j.cell.2017.05.015 · Cited by 1,766
Autophagy maintains stemness by preventing senescence
García-Prat, L., Martínez-Vicente, M., Perdiguero, E., Ortet, L., Rodríguez-Ubreva, J., Rebollo, E., Ruiz-Bonilla, V., Gutarra, S., Ballestar, E., Serrano, A. L., et al. (2016) · Nature · doi:10.1038/nature16187 · Cited by 1,355
Cellular Senescence: Aging, Cancer, and Injury
Calcinotto, A., Kohli, J., Zagato, E., Pellegrini, L., Demaria, M., & Alimonti, A. (2019) · Physiological Reviews · doi:10.1152/physrev.00020.2018 · Cited by 1,270
“Cellular senescence plays important roles in different phases of tumorigenesis such as tumor initiation (OIS), establishment [PTEN loss–induced cellular senescence (PICS), TIS], and escape (258) (FIGURE 4).”
BackgroundSenescence-associated reprogramming promotes cancer stemness
Milanovic, M., Fan, D. N. Y., Belenki, D., Däbritz, J. H. M., Zhao, Z., Yu, Y., Dörr, J. R., Dimitrova, L., Lenze, D., Monteiro Barbosa, I. A., et al. (2018) · Nature · doi:10.1038/nature25167 · Cited by 1,131
Revisiting the hallmarks of cancer.
Fouad, Y. A., & Aanei, C. M. (2017) · Europe PMC (PubMed Central) · Cited by 875
Ribosome biogenesis in cancer: new players and therapeutic avenues
Pelletier, J., Thomas, G., & Volarević, S. (2017) · Nature reviews. Cancer · doi:10.1038/nrc.2017.104 · Cited by 837
A guide to assessing cellular senescence in vitro and in vivo
González‐Gualda, E., Baker, A. G., Fruk, L., & Muñoz‐Espín, D. (2021) · The FEBS Journal · doi:10.1111/febs.15570 · Cited by 645
The dynamic nature of senescence in cancer
Lee, S., & Schmitt, C. A. (2019) · Nature Cell Biology · doi:10.1038/s41556-018-0249-2 · Cited by 588
Cancer-Cell-Intrinsic Mechanisms Shaping the Tumor Immune Landscape
Wellenstein, M. D., & de Visser, K. E. (2018) · Immunity · doi:10.1016/j.immuni.2018.03.004 · Cited by 592
“VillincreERT2;CKIaF/F mice, which display hyper-activated Wnt signaling due to loss of CKIa, exhibit growth arrest of colorectal tumors and induction of senescence, paired with an inflammatory response (Pribluda et al., 2013).”
BackgroundResultAn evolutionary perspective on field cancerization
Curtius, K., Wright, N. A., & Graham, T. A. (2017) · Nature reviews. Cancer · doi:10.1038/nrc.2017.102 · Cited by 540
Stromal senescence establishes an immunosuppressive microenvironment that drives tumorigenesis
Ruhland, M. K., Loza, A. J., Capietto, A.-H., Luo, X., Knolhoff, B. L., Flanagan, K. C., Belt, B. A., Alspach, E., Leahy, K., Luo, J., et al. (2016) · Nature Communications · doi:10.1038/ncomms11762 · Cited by 496
Exercise Attenuates the Major Hallmarks of Aging
Garatachea, N., Pareja-Galeano, H., Sanchis-Gomar, F., Santos-Lozano, A., Fiuza-Luces, C., Morán, M., Emanuele, E., Joyner, M. J., & Lucia, A. (2015) · Rejuvenation Research · doi:10.1089/rej.2014.1623 · Cited by 413
Zhu, X., Chen, Z., Shen, W., Huang, G., Sedivy, J. M., Wang, H., & Ju, Z. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-021-00646-9 · Cited by 425
Clustered miRNAs and their role in biological functions and diseases
Kabekkodu, S. P., Shukla, V., Varghese, V. K., Souza, J. D., Chakrabarty, S., & Satyamoorthy, K. (2018) · Biological reviews/Biological reviews of the Cambridge Philosophical Society · doi:10.1111/brv.12428 · Cited by 364
Oncogenic Roles of the PI3K/AKT/mTOR axis
Aoki, M., & Fujishita, T. (2017) · Current topics in microbiology and immunology · doi:10.1007/82_2017_6 · Cited by 355
“This so-called senescence-associated secretory phonotype (SASP) can help generate both tumor-suppressive and tumorigenic tumor microenvironment (Pérez-Mancera et al. 2014).”
BackgroundVariants of core histones and their roles in cell fate decisions, development and cancer
Buschbeck, M., & Hake, S. B. (2017) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2016.166 · Cited by 362
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Paez‐Ribes, M., González‐Gualda, E., Doherty, G. J., & Muñoz‐Espín, D. (2019) · EMBO Molecular Medicine · doi:10.15252/emmm.201810234 · Cited by 293
“This senescence-associated secretory phenotype (SASP) can play differing roles depending on the physiological context (MuñozEspı́n & Serrano, 2014; Pérez-Mancera et al, 2014).”
BackgroundSenescence-associated secretory phenotype contributes to pathological angiogenesis in retinopathy
Oubaha, M., Miloudi, K., Dejda, A., Guber, V., Mawambo, G., Germain, M.-A., Bourdel, G., Popovic, N., Rezende, F. A., Kaufman, R. J., et al. (2016) · Science Translational Medicine · doi:10.1126/scitranslmed.aaf9440 · Cited by 259
Characterization of novel markers of senescence and their prognostic potential in cancer
Althubiti, M., Lezina, L., Carrera, S., Jukes-Jones, R., Giblett, S. M., Antonov, A., Barlev, N., Saldanha, G. S., Pritchard, C. A., Cain, K., et al. (2014) · Cell Death & Disease · doi:10.1038/cddis.2014.489 · Cited by 256
“Senescence is a well-defined cellular mechanism with a critical role in processes such as ageing(44) and cancer.(45) Despite having been studied for decades, the mechanisms involved in senescence are not fully understood.”
BackgroundCytosolic DNA Sensing in Organismal Tumor Control
Vanpouille-Box, C., Demaria, S., Formenti, S. C., & Galluzzi, L. (2018) · Cancer Cell · doi:10.1016/j.ccell.2018.05.013 · Cited by 250
Melanocytic nevi and melanoma: unraveling a complex relationship
Damsky, W., & Bosenberg, M. (2017) · Oncogene · doi:10.1038/onc.2017.189 · Cited by 263
Mahmud, F., Sarker, D. B., Jocelyn, J. A., & Sang, Q. A. (2024) · Cells · doi:10.3390/cells13211788 · Cited by 272
Sawaki, D., Czibik, G., Pini, M., Ternacle, J., Suffee, N., Mercedes, R., Marcelin, G., Surénaud, M., Marcos, É., Gual, P., et al. (2018) · Circulation · doi:10.1161/circulationaha.117.031358 · Cited by 217
Mechanisms of Selective Autophagy in Normal Physiology and Cancer
Mancias, J. D., & Kimmelman, A. C. (2016) · Journal of Molecular Biology · doi:10.1016/j.jmb.2016.02.027 · Cited by 196
The Role of Autophagy in Cancer
Santana-Codina, N., Mancias, J. D., & Kimmelman, A. C. (2017) · Annual Review of Cancer Biology · doi:10.1146/annurev-cancerbio-041816-122338 · Cited by 214
“Another potential mechanism by which autophagy acts as a tumor suppressor is via its requirement in cellular senescence, a program of permanent cell division arrest that can be induced in response to oncogenic stress to avoid malignant transformation (Pérez-Mancera et al. 2014).”
BackgroundCritical Functions of the Lysosome in Cancer Biology
Davidson, S. M., & Heiden, M. G. V. (2016) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-010715-103101 · Cited by 214
SASP: Tumor Suppressor or Promoter? Yes!
Rao, S. G., & Jackson, J. G. (2016) · Trends in Cancer · doi:10.1016/j.trecan.2016.10.001 · Cited by 206
Integrin Beta 3 Regulates Cellular Senescence by Activating the TGF-β Pathway
Rapisarda, V., Borghesan, M., Miguela, V., Encheva, V., Snijders, A. P., Lujambio, A., & O’Loghlen, A. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.02.012 · Cited by 190
The Cancer SENESCopedia: A delineation of cancer cell senescence
Jochems, F., Thijssen, B., De Conti, G., Jansen, R., Pogacar, Z., Groot, K., Wang, L., Schepers, A., Wang, C., Jin, H., et al. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.109441 · Cited by 201
“The consequence of TIS in the tumor environment is still highly controversial (Lee and Lee, 2014; Pérez-Mancera et al., 2014; Schosserer et al., 2017).”
BackgroundJenke, R., Reßing, N., Hansen, F. K., Aigner, A. M., & Büch, T. (2021) · Cancers · doi:10.3390/cancers13040634 · Cited by 198
Oncogene-induced senescence: a double edged sword in cancer
Liu, X., Ding, J., & Meng, L. (2018) · Acta Pharmacologica Sinica · doi:10.1038/aps.2017.198 · Cited by 204
The Skin Microbiome: Current Landscape and Future Opportunities
Smythe, P., & Wilkinson, H. N. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24043950 · Cited by 218
Saleh, T., Carpenter, V. J., Tyutyunyk‐Massey, L., Murray, G., Leverson, J. D., Souers, A. J., Alotaibi, M. R., Faber, A. C., Reed, J., Harada, H., et al. (2020) · Molecular Oncology · doi:10.1002/1878-0261.12761 · Cited by 190
HMGB2 orchestrates the chromatin landscape of senescence-associated secretory phenotype gene loci
Aird, K. M., Iwasaki, O., Kossenkov, A. V., Tanizawa, H., Fatkhutdinov, N., Bitler, B. G., Le, L., Alicea, G., Yang, T.-L., Johnson, F. B., et al. (2016) · Journal of Cell Biology · doi:10.1083/jcb.201608026 · Cited by 175
“Although the cell cycle arrest phenotype of senescence is tumor suppressive, the detrimental side effects of the SASP have tumor-promoting characteristics and may also play a role in tissue aging (Pérez-Mancera et al., 2014; van Deursen, 2014).”
InfluentialSpatial and Temporal Control of Senescence
Ito, Y., Hoare, M., & Narita, M. (2017) · Trends in Cell Biology · doi:10.1016/j.tcb.2017.07.004 · Cited by 178
Self-citationParacrine roles of cellular senescence in promoting tumourigenesis
Gonzalez-Meljem, J. M., Apps, J. R., Fraser, H. C., & Martinez-Barbera, J. P. (2018) · British Journal of Cancer · doi:10.1038/s41416-018-0066-1 · Cited by 183
Lin, X., Dai, Y., Tong, X., Xu, W., Huang, Q., Jin, X., Li, C., Zhou, F., Zhou, H., Lin, X., et al. (2020) · Redox Biology · doi:10.1016/j.redox.2020.101431 · Cited by 181
“Senescence is a stress response that occurs via a highly conserved mechanism to prevent cells from various stress-induced damage including OS, genotoxic damage and inflammation stimuli [6].”
BackgroundBent, E. H., Gilbert, L. A., & Hemann, M. T. (2016) · Genes & Development · doi:10.1101/gad.284851.116 · Cited by 179
“Chemotherapy-induced DNA damage can cause cellular senescence, an irreversible cell cycle arrest, in both malignant and nonmalignant cells (Perez-Mancera et al. 2014; Klemm and Joyce 2015).”
Michaloglou, C., Crafter, C., Siersbæk, R., Delpuech, O., Curwen, J., Carnevalli, L. S., Staniszewska, A. D., Polanska, U. M., Cheraghchi-Bashi, A., Lawson, M., et al. (2018) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-17-0537 · Cited by 182
“Although both agents induced cell cycle arrest (Supplementary Figure S4A), palbociclib treatment induced a concentration dependent ‘large flat cell’ morphology (Supplementary Figure S4B) and increased β-galactosidase activity (Figure 4B and C), indicative of the induction of a senescence-like phenotype (31, 34, 35).”
BackgroundHaruehanroengra, P., Zheng, Y. Y., Zhou, Y., Huang, Y., & Sheng, J. (2020) · RNA Biology · doi:10.1080/15476286.2020.1722449 · Cited by 178
“of pre-malignant cells [218] which supported that IRBC mediates tumour suppression [219].”
BackgroundCai, H., Scott, E. N., Kholghi, A. O. A., Andreadi, C., Rufini, A., Karmokar, A., Britton, R. G., Horner‐Glister, E., Greaves, P., Jawad, D., et al. (2015) · Science Translational Medicine · doi:10.1126/scitranslmed.aaa7619 · Cited by 179
Cellular Senescence: Molecular Targets, Biomarkers, and Senolytic Drugs
Kudlová, N., Sanctis, J. B. D., & Hajdúch, M. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23084168 · Cited by 186
“Autophagy is a pro-senescence inductor in some cases [17], while in other situations, impaired autophagy can also lead to senescence progression in certain cell types [18].”
BackgroundThe role of lysosomes in cancer development and progression
Tang, T., Yang, Z., Wang, D., Yang, X., Wang, J., Li, L., Wen, Q., Gao, L., Bian, X., & Yu, S. (2020) · Cell & Bioscience · doi:10.1186/s13578-020-00489-x · Cited by 173
mTOR kinase leads to PTEN-loss-induced cellular senescence by phosphorylating p53
Jung, S. H., Hwang, H. J., Kang, D., Park, H. A., Lee, H. C., Jeong, D., Lee, K., Park, H. J., Ko, Y.-G., & Lee, J.-S. (2019) · Oncogene · doi:10.1038/s41388-018-0521-8 · Cited by 166
Nishimura, K., Kumazawa, T., Kuroda, T., Katagiri, N., Tsuchiya, M., Goto, N., Furumai, R., Murayama, A., Yanagisawa, J., & Kimura, K. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.01.055 · Cited by 167
Cancer cells enter dormancy after cannibalizing mesenchymal stem/stromal cells (MSCs)
Bartosh, T. J., Ullah, M., Zeitouni, S., Beaver, J., & Prockop, D. J. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1612290113 · Cited by 169
DNA damage response (DDR) and senescence: shuttled inflamma-miRNAs on the stage of inflamm-aging
Olivieri, F., Albertini, M. C., Orciani, M., Ceka, A., Cricca, M., Procopio, A. D., & Bonafè, M. (2015) · Oncotarget · doi:10.18632/oncotarget.5899 · Cited by 163
“Senescence per se has long been known to be a mechanism halting the replication of cells that have acquired potentially hazardous genetic mutations [2, 14].”
BackgroundA step-by-step microRNA guide to cancer development and metastasis
Markopoulos, G. S., Roupakia, E., Tokamani, M., Chavdoula, E., Hatziapostolou, M., Polytarchou, C., Marcu, K. B., Papavassiliou, A. G., Sandaltzopoulos, R., & Kolettas, E. (2017) · Cellular Oncology · doi:10.1007/s13402-017-0341-9 · Cited by 164
“Cells acquiring oncogenic driver mutations undergo oncogene-induced replication stress leading to premature senescence that is established by de-repression of the INK4/ARF locus, which acts as a sensor to link stress with pRb (p16-pRB) and p53 (p14p53-p21) tumor suppressor networks [116, 117, 130, 131].”
BackgroundCell Senescence, DNA Damage, and Metabolism
Shmulevich, R., & Krizhanovsky, V. (2021) · Antioxidants & Redox Signaling · doi:10.1089/ars.2020.8043 · Cited by 157
“Since SASP may cause both beneficial and harmful consequences, it may thus serve as a potent, dual-edged target for human disease pharmaceutical intervention (2, 74).”
When dormancy fuels tumour relapse
Santos-de-Frutos, K., & Djouder, N. (2021) · Communications Biology · doi:10.1038/s42003-021-02257-0 · Cited by 153
Immune checkpoint blockade therapy
Wieder, T., Eigentler, T., Brenner, E., & Röcken, M. (2018) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2018.02.042 · Cited by 134
Intermittent hypoxia induces a metastatic phenotype in breast cancer
Chen, A., Sceneay, J., Gödde, N., Kinwel, T., Ham, S., Thompson, E. W., Humbert, P. O., & Möller, A. (2018) · Oncogene · doi:10.1038/s41388-018-0259-3 · Cited by 133
Brenner, E., Schörg, B. F., Ahmetlić, F., Wieder, T., Hilke, F. J., Simon, N., Schroeder, C., Demidov, G. M., Riedel, T., Fehrenbacher, B., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-14987-6 · Cited by 136
Targeting 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
“Hence, cell-to-cell communications—mainly through the paracrine effects of secreted factors by the SASP affecting surrounding cell and tissue—better explains the participation of cellular senescence in various physiological and pathological processes in contrast to the lone proliferative arrest [13].”
BackgroundLesina, 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
Calcium signaling and cellular senescence
Martin, N., & Bernard, D. (2017) · Cell Calcium · doi:10.1016/j.ceca.2017.04.001 · Cited by 133
LB100, a small molecule inhibitor of PP2A with potent chemo- and radio-sensitizing potential
Hong, C. S., Ho, W. S., Zhang, C., Yang, C., Elder, J. B., & Zhengping, Z. (2015) · Cancer Biology & Therapy · doi:10.1080/15384047.2015.1040961 · Cited by 125
“In particular, tumor cell senescence is a major contributor to treatment resistance, particularly with radiotherapy and conventional DNA-damaging chemo-agents that preferentially affect actively dividing cells.(50,51) Essential to cell senescence is proper functioning of PP2A during the G2 phase, during which Ras sign…”
BackgroundCell senescence is an antiviral defense mechanism
Baz-Martínez, M., Da Silva-Álvarez, S., Rodríguez, E., Guerra, J., El Motiam, A., Vidal, A., García-Caballero, T., González-Barcia, M., Sánchez, L., Muñoz-Fontela, C., et al. (2016) · Scientific Reports · doi:10.1038/srep37007 · Cited by 103
DDR-mediated crosstalk between DNA-damaged cells and their microenvironment
Malaquin, N., Carrier-Leclerc, A., Dessureault, M., & Rodier, F. (2015) · Frontiers in Genetics · doi:10.3389/fgene.2015.00094 · Cited by 124
“MINI REVIEW published: 12 March 2015 doi: 10.3389/fgene.2015.00094 Edited by: Antonio Porro, University of Zurich, Switzerland Reviewed by: David Raulet, University of California, Berkeley, USA Alessandra Montecucco,”
BackgroundInfluentialRheumatoid Arthritis, Immunosenescence and the Hallmarks of Aging
Chalan, P., van den Berg, A., Kroesen, B., Brouwer, L., & Boots, A. M. H. (2015) · Current Aging Science · doi:10.2174/1874609808666150727110744 · Cited by 117
“Support for this notion comes from studies demonstrating that NK-cells clear senescent cells in tumor lesions [63] and eliminate senescent cells involved in tissue damage [64].”
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
ZEB 1‐regulated inflammatory phenotype in breast cancer cells
Katsura, A., Tamura, Y., Hokari, S., Harada, M., Morikawa, M., Sakurai, T., Takahashi, K., Mizutani, A., Nishida, J., Yokoyama, Y., et al. (2017) · Molecular Oncology · doi:10.1002/1878-0261.12098 · Cited by 114
“IL-6, IL-8, and some other ZEB1-regulated secretory proteins are related to the senescence-associated secretory phenotype (Perez-Mancera et al., 2014).”
BackgroundDiverse functions of miR-373 in cancer
Wei, F., Cao, C., Xu, X., & Wang, J. (2015) · Journal of Translational Medicine · doi:10.1186/s12967-015-0523-z · Cited by 110
“However, by inactivation of tumor suppressors involved in senescence, such as P53 and RB, transformed cells overcome this barrier and reacquire proliferative capacity [39].”
BackgroundNelson, 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
“Background Cellular senescence is a stable proliferation arrest associated with an altered pro-inflammatory secretory pathway and an important tumor suppressor mechanism [1, 2].”
BackgroundCellular Senescence and Ageing: Mechanisms and Interventions
Mylonas, A., & O’Loghlen, A. (2022) · Frontiers in Aging · doi:10.3389/fragi.2022.866718 · Cited by 114
Ras signaling through RASSF proteins
Donninger, H., Schmidt, M., Mezzanotte-Sharpe, J., Barnoud, T., & Clark, G. J. (2016) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2016.06.007 · Cited by 110
Abdul-Aziz, A. M., Sun, Y., Hellmich, C., Marlein, C. R., Mistry, J., Forde, E., Piddock, R. E., Shafat, M. S., Morfakis, A., Mehta, T., et al. (2019) · Blood · doi:10.1182/blood-2018-04-845420 · Cited by 105
To clear, or not to clear (senescent cells)? That is the question
Lujambio, A. (2016) · BioEssays · doi:10.1002/bies.201670910 · Cited by 108
The impact of cellular senescence in skin ageing: A notion of mosaic and therapeutic strategies
Toutfaire, M., Bauwens, É., & Debacq‐Chainiaux, F. (2017) · Biochemical Pharmacology · doi:10.1016/j.bcp.2017.04.011 · Cited by 107
“The recruitment of immune effector cells to the lesion may not only kill senescent tumour cells but also non-senescent ones [19].”
Targeting Senescent Cells in Fibrosis: Pathology, Paradox, and Practical Considerations
Schafer, M. J., Haak, A. J., Tschumperlin, D. J., & LeBrasseur, N. K. (2018) · Current Rheumatology Reports · doi:10.1007/s11926-018-0712-x · Cited by 106
NUPR1 maintains autolysosomal efflux by activatingSNAP25transcription in cancer cells
Mu, Y., Yan, X., Li, D., Zhao, D., Wang, L., Wang, X., Gao, D., Yang, J., Zhang, H., Li, Y., et al. (2017) · Autophagy · doi:10.1080/15548627.2017.1338556 · Cited by 105
“Cellular senescence is now widely considered to be an integrated and common phenotype that is potentially important for tumor development, tumor suppression, and response to therapy [47].”
BackgroundChemotherapy-induced senescence, an adaptive mechanism driving resistance and tumor heterogeneity
Guillon, J., Petit, C., Toutain, B., Guette, C., Lelièvre, E., & Coqueret, O. (2019) · Cell Cycle · doi:10.1080/15384101.2019.1652047 · Cited by 102
“[1] Perez-Mancera PA, Young AR, Narita M.”
BackgroundAssouline, B., Kahn, R., Hodali, L., Condiotti, R., Engel, Y., Elyada, E., Mordechay‐Heyn, T., Pitarresi, J. R., Atias, D., Steinberg, E., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-50441-7 · Cited by 105
Cellular 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
Connecting the dots: therapy-induced senescence and a tumor-suppressive immune microenvironment
Vilgelm, A. E., Johnson, C. A., Prasad, N., Yang, J., Chen, S.-C., Ayers, G. D., Pawlikowski, J. S., Raman, D., Sosman, J. A., Kelley, M., et al. (2016) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djv406 · Cited by 95
“Senescence can be induced in cancer cells upon treatment with a variety of drugs (11,12) and termed therapy-induced senescence (TIS).”
BackgroundInfluentialKolodkin‐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
Petri, R. M., Hackel, A. M., Hahnel, K., Dumitru, C. A., Bruderek, K., Flohé, S. B., Paschen, A., Lang, S., & Brandau, S. (2017) · Stem Cell Reports · doi:10.1016/j.stemcr.2017.06.020 · Cited by 91
“Senescent-like NK Cells Favor MSC Functions, which Are Associated with Tissue Regeneration SASP released by decidual NK cells has been reported to stimulate angiogenesis (Rajagopalan and Long, 2012), which requires the coordinated response of stromal and endothelial cells.”
BackgroundInfluentialThe Senescence–Stemness Alliance – A Cancer-Hijacked Regeneration Principle
Milanovic, M., Yu, Y., & Schmitt, C. A. (2018) · Trends in Cell Biology · doi:10.1016/j.tcb.2018.09.001 · Cited by 92
Premature cell senescence in human skin: Dual face in chronic acquired pigmentary disorders
Bellei, B., & Picardo, M. (2019) · Ageing Research Reviews · doi:10.1016/j.arr.2019.100981 · Cited by 93
Regulation of senescence escape by TSP1 and CD47 following chemotherapy treatment
Guillon, J., Petit, C., Moreau, M., Toutain, B., Henry, C., Roché, H., Bonichon-Lamichhane, N., Salmon, J. P., Lemonnier, J., Campone, M., et al. (2019) · Cell Death & Disease · doi:10.1038/s41419-019-1406-7 · Cited by 90
Non-Cell-Autonomous Regulation of Cellular Senescence in Cancer
Mitri, D. D., & Alimonti, A. (2015) · Trends in Cell Biology · doi:10.1016/j.tcb.2015.10.005 · Cited by 92
Yuan, D., Luo, J., Sun, Y., Hao, L., Zheng, J., & Yang, Z. (2021) · Cellular Signalling · doi:10.1016/j.cellsig.2021.110030 · Cited by 88
mTOR Activity and Autophagy in Senescent Cells, a Complex Partnership
Cayo, Á., Segovia, R., Venturini, W., Moore‐Carrasco, R., Valenzuela, C. A., & Brown, N. E. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22158149 · Cited by 96
Takebayashi, S., Tanaka, H., Hino, S., Nakatsu, Y., Igata, T., Sakamoto, A., Narita, M., & Nakao, M. (2015) · Aging Cell · doi:10.1111/acel.12351 · Cited by 84
“Interestingly, RB is required for SAHF formation through cooperation with histone chaperone proteins HIRA and antisilencing function 1A (Narita et al., 2003; Ye et al., 2007).”
BackgroundInfluentialSelf-citationImmune recognition of irradiated cancer cells
Wennerberg, E., Vanpouille‐Box, C., Bornstein, S., Yamazaki, T., Demaria, S., & Galluzzi, L. (2017) · Immunological Reviews · doi:10.1111/imr.12568 · Cited by 88
Shen, W., Liu, L., & Zeng, S. (2018) · Cancer translational medicine · doi:10.4103/ctm.ctm_22_18 · Cited by 92
Endoplasmic reticulum quality control in cancer: Friend or foe
Kim, H., Bhattacharya, A., & Qi, L. (2015) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2015.02.003 · Cited by 87
Short-term gain, long-term pain: the senescence life cycle and cancer
Chan, A. S. L., & Narita, M. (2019) · Genes & Development · doi:10.1101/gad.320937.118 · Cited by 80
“…of senescence can be seen in OIS, where some “mitogenic” oncogenes (or loss of tumor suppressors, as exemplified by PTEN loss-induced cellular senescence [PICS]) can paradoxically induce persistent proliferative arrest (Braig and Schmitt 2006; Courtois-Cox et al. 2008; Pérez-Mancera et al. 2014).”
BackgroundInfluentialSelf-citationAutophagy-induced senescence is regulated by p38α signaling
Slobodnyuk, K., Radic, N., Ivanova, S., Lladó, A., Trempolec, N., Antonio Zorzano, A., & Nebreda, Á. R. (2019) · Cell Death and Disease · doi:10.1038/s41419-019-1607-0 · Cited by 93
Autophagy at the intersection of aging, senescence, and cancer
Cassidy, L. D., & Narita, M. (2022) · Molecular Oncology · doi:10.1002/1878-0261.13269 · Cited by 93
Self-citationDocetaxel-induced polyploidization may underlie chemoresistance and disease relapse
Ogden, A., Rida, P. C. G., Knudsen, B. S., Kucuk, O., & Aneja, R. (2015) · Cancer Letters · doi:10.1016/j.canlet.2015.06.025 · Cited by 87
“protective, anti-cancer mechanism [24], so systemic antagonism of this process may have the potential to promote carcinogenesis.”
A matter of life and death: stem cell survival in tissue regeneration and tumour formation
Soteriou, D., & Fuchs, Y. (2018) · Nature Reviews Cancer · doi:10.1038/nrc.2017.122 · Cited by 87
Numb is required to prevent p53-dependent senescence following skeletal muscle injury
Le Roux, I., Konge, J., Le Cam, L., Flamant, P., & Tajbakhsh, S. (2015) · Nature Communications · doi:10.1038/ncomms9528 · Cited by 81
Exosomes and Other Extracellular Vesicles in HPV Transmission and Carcinogenesis
Guenat, D., Hermetet, F., Prétet, J., & Mougin, C. (2017) · Viruses · doi:10.3390/v9080211 · Cited by 80
“This is probably why senescence is associated with cancer progression in certain circumstances [104], and secretion of IAP family protein-enriched Exos (especially when E6/E7 are targeted in HPV-associated cancer) may participate in tumor development/progression.”
BackgroundProtein Acyltransferase DHHC3 Regulates Breast Tumor Growth, Oxidative Stress, and Senescence
Sharma, C., Wang, H.-X., Li, Q., Knoblich, K., Reisenbichler, E., Richardson, A. L., & Hemler, M. E. (2017) · Cancer Research · doi:10.1158/0008-5472.can-17-1536 · Cited by 84
“3B) emulates a senescence-associated secretory phenotype (SASP) response, which triggers innate immune cell recruitment, and facilitates tumor clearance (11).”
BackgroundThe Evolving, Multifaceted Roles of Autophagy in Cancer
Liu, J., & Debnath, J. (2016) · Advances in cancer research · doi:10.1016/bs.acr.2016.01.005 · Cited by 82
Targeting the interleukin-1 pathway in patients with hematological disorders
de Mooij, C. E. M., Netea, M. G., van der Velden, W. J. F. M., & Blijlevens, N. M. A. (2017) · Blood · doi:10.1182/blood-2016-12-754994 · Cited by 79
Reconstructing the molecular life history of gliomas
Barthel, F. P., Wesseling, P., & Verhaak, R. G. W. (2018) · Acta Neuropathologica · doi:10.1007/s00401-018-1842-y · Cited by 86
“The role of senescence in cancer has been reviewed extensively [29, 42, 78, 83, 174, 193].”
BackgroundZhao, L., Hu, K., Cao, J., Wang, P., Li, J., Zeng, K., He, X., Tu, P., Tong, T., & Han, L. (2019) · Aging · doi:10.18632/aging.102240 · Cited by 79
“Cellular senescence is defined as a state of irreversible growth arrest and leads to a senescent phenotype, which is characterized by upregulated senescence-associated βgalactosidase (SA-β-gal) activity, cell cycle arrest and cell proliferation inhibition [6, 7].”
BackgroundTrial Watch: Immunotherapy plus radiation therapy for oncological indications
Vacchelli, E., Bloy, N., Aranda, F., Buqué, A., Cremer, I., Demaria, S., Eggermont, A. M. M., Formenti, S. C., Fridman, W. H., Fucikova, J. P., et al. (2016) · OncoImmunology · doi:10.1080/2162402x.2016.1214790 · Cited by 76
“nant astrocytes that underlie (at least in part) the pronounced radio- and chemoresistance of astrocytomas;(109) (8) Reid and”
BackgroundInfluential
Metadata
- Authors
- Pérez-Mancera, P. A., Young, A. R. J., & Narita, M.
- Affiliations
- University of Cambridge (GB)
- Corresponding author
- Narita, Masashi
- Venue
- Nature Reviews Cancer
- Published
- 2014-07-17
- Volume
- 14
- Issue
- 8
- Pages
- 547-558
- ISSN
- 1474-175X (ISSN-L)
- 1474-1768
- OpenAlex
- W1963704214
- Semantic Scholar
- 34d61b9672e8adfeea27bec14cd0bfbd47df2729
- Cited by
- 462
- References
- 161
- Citations by year
- 2026: 9 · 2025: 26 · 2024: 32 · 2023: 35 · 2022: 41 · 2021: 39 · 2020: 34 · 2019: 41 · 2018: 48 · 2017: 58 · 2016: 55 · 2015: 39 · 2014: 5
- FWCI
- 6.14
- Type
- journal article
- Language
- en
- Open access
- Locations
- Nature reviews. Cancer (publishedVersion)
- PubMed (publishedVersion)
- Apollo (University of Cambridge) (submittedVersion)
- Funders
- Cancer Research UK (15890)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Keywords
- cellular senescence, senescence-associated secretory phenotype, carcinogenesis, tumor progression, tumor suppression, tumor promotion, cell cycle arrest, non-cell-autonomous effects, cancer therapy response
- MeSH terms
- Animals, Humans, Neoplasms, Precancerous Conditions, Signal Transduction, Cellular Senescence, Tumor Microenvironment
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