Notch Signaling Mediates Secondary Senescence

Yee Voan Teo, Nattaphong Rattanavirotkul, Nelly Olova, Angela Salzano, Andrea Quintanilla, Nuria Tarrats, Christos Kiourtis, Miryam Müller, Anthony R. Green, Peter D Adams, Juan-Carlos Acosta, Tom Bird, Kristina Kirschner, Nicola Neretti, Tamir Chandra

Research output: Contribution to journalArticlepeer-review

Abstract

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.
Original languageEnglish
Pages (from-to)997-1007.e5
Number of pages17
JournalCell Reports
Volume27
Issue number4
DOIs
Publication statusPublished - 23 Apr 2019

Fingerprint Dive into the research topics of 'Notch Signaling Mediates Secondary Senescence'. Together they form a unique fingerprint.

Cite this