A complex secretory program orchestrated by the inflammasome controls paracrine senescence

Acosta, Juan Carlos; Banito, Ana; Wuestefeld, Torsten; Georgilis, Athena; Janich, Peggy, 1981-; Morton, Jennifer P.; Athineos, Dimitris; Kang, Tae-Won; Lasitschka, Felix; Andrulis, Mindaugas; Pascual, Gloria; Morris, Kelly J.; Khan, Sadaf; Jin, Hong; Dharmalingam, Gopuraja; Snijders, Ambrosius P.; Carroll, Thomas; Capper, David; Pritchard, Catrin; Inman, Gareth J.; Longerich, Thomas; Sansom, Owen J.; Aznar Benitah, Salvador; Zender, Lars; Gil, Jesús

A complex secretory program orchestrated by the inflammasome controls paracrine senescence

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dc.contributor.author Acosta, Juan Carlosca
dc.contributor.author Banito, Anaca
dc.contributor.author Wuestefeld, Torstenca
dc.contributor.author Georgilis, Athenaca
dc.contributor.author Janich, Peggy, 1981-ca
dc.contributor.author Morton, Jennifer P.ca
dc.contributor.author Athineos, Dimitrisca
dc.contributor.author Kang, Tae-Wonca
dc.contributor.author Lasitschka, Felixca
dc.contributor.author Andrulis, Mindaugasca
dc.contributor.author Pascual, Gloriaca
dc.contributor.author Morris, Kelly J.ca
dc.contributor.author Khan, Sadafca
dc.contributor.author Jin, Hongca
dc.contributor.author Dharmalingam, Gopurajaca
dc.contributor.author Snijders, Ambrosius P.ca
dc.contributor.author Carroll, Thomasca
dc.contributor.author Capper, Davidca
dc.contributor.author Pritchard, Catrinca
dc.contributor.author Inman, Gareth J.ca
dc.contributor.author Longerich, Thomasca
dc.contributor.author Sansom, Owen J.ca
dc.contributor.author Aznar Benitah, Salvadorca
dc.contributor.author Zender, Larsca
dc.contributor.author Gil, Jesúsca
dc.date.accessioned 2014-06-03T11:02:02Z
dc.date.available 2014-06-03T11:02:02Z
dc.date.issued 2013ca
dc.description.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.
dc.description.sponsorship Core support from the MRC and grants from MRCT, CRUK and the AICR financially supported the research in J.G's laboratory. J.G. is also supported by the EMBO Young Investigator Programme
dc.format.mimetype application/pdfca
dc.identifier.citation Acosta JC, Banito A, Wuestefeld T, Georgilis A, Janich P, Morton JP et al. A complex secretory program orchestrated by the inflammasome controls paracrine senescence. Nat Cell Biol. 2013;15(8):978-90. DOI: 10.1038/ncb2784ca
dc.identifier.doi http://dx.doi.org/10.1038/ncb2784
dc.identifier.issn 1465-7392ca
dc.identifier.uri http://hdl.handle.net/10230/22558
dc.language.iso engca
dc.publisher Nature Publishing Groupca
dc.relation.ispartof Nature Cell Biology. 2013;15(8):978-90
dc.rights.accessRights info:eu-repo/semantics/openAccessca
dc.subject.other Cèl·lules -- Envelliment
dc.subject.other Tumors
dc.title A complex secretory program orchestrated by the inflammasome controls paracrine senescenceca
dc.type info:eu-repo/semantics/articleca
dc.type.version info:eu-repo/semantics/acceptedVersionca

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