A complex secretory program orchestrated by the inflammasome controls paracrine senescence
Juan Carlos Acosta,Ana Banito,Torsten Wuestefeld,Athena Georgilis,Peggy Janich,Jennifer P. Morton,Dimitris Athineos,Tae-Won Kang,Felix Lasitschka,Mindaugas Andrulis,Gloria Pascual,Kelly J. Morris,Sadaf Khan,Hong Jin,Gopuraja Dharmalingam,Ambrosius P. Snijders,Thomas L. Carroll,David Capper,Catrin Pritchard,Gareth J. Inman,Thomas Longerich,Owen J. Sansom,Salvador Aznar Benitah,Lars Zender,Jesús Gil +24 more
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TLDR
It is demonstrated that the SASP can cause paracrine senescence and impact on tumour suppression andSenescence in vivo and TGF-β ligands play a major role by regulating p15INK4b and p21CIP1.Abstract:
Oncogene-induced senescence (OIS) is crucial for tumour suppression. Senescent cells implement a complex pro-inflammatory response termed the senescence-associated secretory phenotype (SASP). The SASP reinforces senescence, activates immune surveillance and paradoxically also has pro-tumorigenic properties. Here, we present evidence that the SASP can also induce paracrine senescence in normal cells both in culture and in human and mouse models of OIS in vivo. Coupling quantitative proteomics with small-molecule screens, we identified multiple SASP components mediating paracrine senescence, including TGF-β family ligands, VEGF, CCL2 and CCL20. Amongst them, TGF-β ligands play a major role by regulating p15(INK4b) and p21(CIP1). Expression of the SASP is controlled by inflammasome-mediated IL-1 signalling. The inflammasome and IL-1 signalling are activated in senescent cells and IL-1α expression can reproduce SASP activation, resulting in senescence. Our results demonstrate that the SASP can cause paracrine senescence and impact on tumour suppression and senescence in vivo.read more
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Senescent cells spread the word: non-cell autonomous propagation of cellular senescence.
TL;DR: It now seems senescence can be transmitted in a paracrine fashion in several in vitro and in vivo contexts, and these new findings may have interesting implications for tissue homeostasis and future cancer therapies.
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Activation of epidermal growth factor receptor signaling mediates cellular senescence induced by certain pro-inflammatory cytokines.
TL;DR: It is reported that certain pro‐inflammatory cytokines induce cellular senescence through activation of the EGFR‐Ras signaling pathway, and this study offers new insight into a long‐ignored mechanism by which EGFR could regulate cellularsenescence and suggests that growth signals themselves may catalyze aging under certain conditions.
Journal ArticleDOI
TGF-β Signaling Accelerates Senescence of Human Bone-Derived CD271 and SSEA-4 Double-Positive Mesenchymal Stromal Cells.
Hiroshi Kawamura,Ryusuke Nakatsuka,Yoshikazu Matsuoka,Keisuke Sumide,Tatsuya Fujioka,Hiroaki Asano,Hirokazu Iida,Yoshiaki Sonoda +7 more
TL;DR: The results suggest that, in part, old DPMSCs accelerate cellular senescence through TGF-β signaling, which is generally thought to decline with age.
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Oncogene-Expressing Senescent Melanocytes Up-Regulate MHC Class II, a Candidate Melanoma Suppressor Function.
John van Tuyn,Farah Jaber-Hijazi,Douglas J. MacKenzie,John J. Cole,Elizabeth R. Mann,Jeff S. Pawlikowski,Taranjit Singh Rai,David M. Nelson,Tony McBryan,Andre Ivanov,Karen Blyth,Hong Wu,Simon Milling,Peter D. Adams,Peter D. Adams +14 more
TL;DR: It is proposed that engagement of OIS in primary human melanocytes is accompanied by an antigen presentation phenotype, likely to promote tumor suppression via activation of the adaptive immune system.
Journal ArticleDOI
Cellular lifespan and senescence: a complex balance between multiple cellular pathways
TL;DR: It is concluded that cellular lifespan and senescence are complex concepts that are governed by multiple independent and interdependent pathways, and that greater understanding of these pathways, their interactions and their convergence upon specific cellular phenotypes may lead to viable therapies for tissue regeneration and treatment of age‐related pathologies, which are caused by or exacerbated by senescent cells in vivo.
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