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Notch Signaling Mediates Secondary Senescence

Published on Apr 1, 2019in Cell Reports7.815
· DOI :10.1016/j.celrep.2019.03.104
Yee Voan Teo3
Estimated H-index: 3
(Brown University),
Nattaphong Rattanavirotkul1
Estimated H-index: 1
(Edin.: University of Edinburgh)
+ 12 AuthorsTamir Chandra17
Estimated H-index: 17
(Edin.: University of Edinburgh)
Abstract
Summary Oncogene-induced senescence (OIS) is a tumor suppressive response to oncogene activation that can be transmitted to neighboring cells through secreted factors of the senescence-associated secretory phenotype (SASP). Currently, primary and secondary senescent cells are not considered functionally distinct endpoints. Using single-cell analysis, we observed two distinct transcriptional endpoints, a primary endpoint marked by Ras and a secondary endpoint marked by Notch activation. We find that secondary oncogene-induced senescence in vitro and in vivo requires Notch, rather than SASP alone, as previously thought. Moreover, Notch signaling weakens, but does not abolish, SASP in secondary senescence. Global transcriptomic differences, a blunted SASP response, and the induction of fibrillar collagens in secondary senescence point toward a functional diversification between secondary and primary senescence.
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