A complex secretory program orchestrated by the inflammasome controls paracrine senescence.

Details

Serval ID
serval:BIB_8D8945CB1AD7
Type
Article: article from journal or magazin.
Collection
Publications
Title
A complex secretory program orchestrated by the inflammasome controls paracrine senescence.
Journal
Nature Cell Biology
Author(s)
Acosta J.C., Banito A., Wuestefeld T., Georgilis A., Janich P., Morton J.P., Athineos D., Kang T.W., Lasitschka F., Andrulis M., Pascual G., Morris K.J., Khan S., Jin H., Dharmalingam G., Snijders A.P., Carroll T., Capper D., Pritchard C., Inman G.J., Longerich T., Sansom O.J., Benitah S.A., Zender L., Gil J.
ISSN
1476-4679 (Electronic)
ISSN-L
1465-7392
Publication state
Published
Issued date
2013
Volume
15
Number
8
Pages
978-990
Language
english
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.
Pubmed
Web of science
Create date
25/06/2013 12:46
Last modification date
20/08/2019 15:51
Usage data