Notch Signaling Mediates Secondary Senescence.
Cell Rep
; 27(4): 997-1007.e5, 2019 04 23.
Article
en En
| MEDLINE
| ID: mdl-31018144
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Senescencia Celular
/
Receptores Notch
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Cell Rep
Año:
2019
Tipo del documento:
Article
País de afiliación:
Estados Unidos