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A complex secretory program orchestrated by the inflammasome controls paracrine senescence

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 pro...

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Main Authors: Acosta, Juan-Carlos (Author) , Banito, Ana (Author) , Wuestefeld, Torsten (Author) , Georgilis, Athena (Author) , Janich, Peggy (Author) , Morton, Jennifer P. (Author) , Athineos, Dimitris (Author) , Kang, Tae-Won (Author) , Lasitschka, Felix (Author) , Andrulis, Mindaugas (Author) , Pascual, Gloria (Author) , Morris, Kelly J. (Author) , Khan, Sadaf (Author) , Jin, Hong (Author) , Dharmalingam, Gopuraja (Author) , Snijders, Ambrosius P. (Author) , Carroll, Thomas (Author) , Capper, David (Author) , Pritchard, Catrin (Author) , Inman, Gareth J. (Author) , Longerich, Thomas (Author) , Sansom, Owen J. (Author) , Benitah, Salvador Aznar (Author) , Zender, Lars (Author) , Gil, Jesús (Author)
Format: Article (Journal)
Language:English
Published: 16 June 2013
In: Nature cell biology
Year: 2013, Volume: 15, Issue: 8, Pages: 978-990
ISSN:1476-4679
DOI:10.1038/ncb2784
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1038/ncb2784
Verlag, lizenzpflichtig, Volltext: https://www.nature.com/articles/ncb2784
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Author Notes: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 Carroll, David Capper, Catrin Pritchard, Gareth J. Inman, Thomas Longerich, Owen J. Sansom, Salvador Aznar Benitah, Lars Zender, and Jesús Gil
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Summary: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 p15INK4b and p21CIP1. 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.
Item Description:Gesehen am 05.05.2021
Physical Description:Online Resource
ISSN:1476-4679
DOI:10.1038/ncb2784

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