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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Dysfunction of the circadian transcriptional factor CLOCK in mice resists chemical carcinogen-induced tumorigenesis
Ken ichi Hashikawa,Chiharu Katamune,Naoki Kusunose,Naoya Matsunaga,Satoru Koyanagi,Shigehiro Ohdo +5 more
TL;DR: Genetic and biochemical experiments revealed that the suppression of EGF receptor-mediated signal transduction in DMBA-treated Clk/Clk mice was associated with the expression of the cellular senescence factor p16INK4a, suggesting an uncovered role for CLOCK in the development of chemical carcinogen-induced primary tumors.
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Role of Senescent Renal Cells in Pathophysiology of Diabetic Kidney Disease.
TL;DR: Current literature linking senescence to DKD is reviewed and the likely routes to intervention in a clinical setting are speculated, with senescent cells an appealing target for intervention in these disorders.
Journal ArticleDOI
Senescence and Cancer: Role of Nitric Oxide (NO) in SASP.
Nesrine Mabrouk,Nesrine Mabrouk,Silvia Ghione,Silvia Ghione,Véronique Laurens,Véronique Laurens,Stéphanie Plenchette,Stéphanie Plenchette,Ali Bettaieb,Ali Bettaieb,Catherine Paul,Catherine Paul +11 more
TL;DR: The modulatory effect of nitric oxide (NO) in SASP and the possible benefits of the use of NO donors or iNOS inducers in combination with senotherapy in cancer treatment are discussed.
Journal ArticleDOI
The Interaction of the Senescent and Adjacent Breast Cancer Cells Promotes the Metastasis of Heterogeneous Breast Cancer Cells through Notch Signaling.
Na Zhang,Jiafei Ji,Dandan Zhou,Xuan Liu,Xinglin Zhang,Yingqi Liu,Weifang Xiang,Meida Wang,Lian Zhang,Guannan Wang,Baiqu Huang,Jun Lu,Yu Zhang +12 more
TL;DR: In this article, the authors used doxorubicin to induce senescence in breast cancer cells, followed by a co-culture of the cells with conditional media of non-senescent cells and directly with senescent cells.
Journal ArticleDOI
The crosstalk between cellular reprogramming and senescence in aging and regeneration.
Aurélie Chiche,Cheng Chen,Han Li +2 more
TL;DR: Recent studies on the interplay between cellular senescence and reprogramming are reviewed to discuss how both strategies could impact aging process and the possibility of combine them for more efficient regeneration and rejuvenation.
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