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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Dissertation
Pancreatic Dysfunction in Shwachman-Diamond Syndrome
TL;DR: Shwachman-Diamond syndrome is an autosomal recessive ribosomopathy caused by loss of the ancillary translation factor ShwachMan-Bodian- Diamond syndrome protein, which functions in ribosome subunit joining and protein synthesis.
Journal ArticleDOI
Tumor cell malignancy: A complex trait built through reciprocal interactions between tumors and tissue-body system
TL;DR: In this paper , the authors define malignancy as a complex genetic trait incorporating genetically determined reciprocal interactions between tumor cells and tissue-body ecosystem, and take the option of defining malignant traits as complex genetic traits.
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Senescence of alveolar epithelial cells impacts initiation and chronic phases of murine fibrosing interstitial lung disease
Zento Yamada,Junko Nishio,Kaori Motomura,Satoshi Mizutani,Soichi Yamada,Tetuo Mikami,Toshihiro Nanki +6 more
TL;DR: It is demonstrated that p21WAF1/CIP1- and p16INK4A-pathway-dependent senescence in type 2 alveolar epithelial cells (AEC2) were both involved in the initiation and progression of lung fibrosis in murine bleomycin (BLM)-induced ILD and provides insights into its pathogenesis, which may lead to the development of new therapeutic methods targeting senescent cells or SASP molecules.
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Irradiation Accelerates Plaque Formation and Cellular Senescence in Flow-Altered Carotid Arteries of Apolipoprotein E Knock-Out Mice.
Yu Yamamoto,Manabu Minami,Kazumichi Yoshida,Manabu Nagata,Takeshi Miyata,Tao Yang,Naoki Takayama,Keita Suzuki,Masakazu Okawa,Kiyofumi Yamada,Susumu Miyamoto +10 more
TL;DR: The senescence-associated secretory phenotype is a mechanism of various organ diseases, including atherosclerosis as discussed by the authors, and it is the mechanism of chronic inflammation through cellular senescences.
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Aging and Cancer: The Waning of Community Bonds.
TL;DR: In this paper, the authors argue that a major contribution of aging towards increasing the risk of neoplastic disease is conveyed through effects on the microenvironment, which leads to a generalized decrease in proliferative fitness, favoring the emergence of more competitive variant clones.
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