The variant senescence-associated secretory phenotype induced by centrosome amplification constitutes a pathway that activates hypoxia-inducible factor-1α.
Aging Cell
; 22(3): e13766, 2023 03.
Article
em En
| MEDLINE
| ID: mdl-36660875
ABSTRACT
The senescence-associated secretory phenotype (SASP) can promote paracrine invasion while suppressing tumour growth, thus generating complex phenotypic outcomes. Likewise, centrosome amplification can induce proliferation arrest yet also facilitate tumour invasion. However, the eventual fate of cells with centrosome amplification remains elusive. Here, we report that centrosome amplification induces a variant of SASP, which constitutes a pathway activating paracrine invasion. The centrosome amplification-induced SASP is non-canonical as it lacks the archetypal detectable DNA damage and prominent NF-κB activation, but involves Rac activation and production of reactive oxygen species. Consequently, it induces hypoxia-inducible factor 1α and associated genes, including pro-migratory factors such as ANGPTL4. Of note, cellular senescence can either induce tumourigenesis through paracrine signalling or conversely suppress tumourigenesis through p53 induction. By analogy, centrosome amplification-induced SASP may therefore be one reason why extra centrosomes promote malignancy in some experimental models but are neutral in others.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fenótipo Secretor Associado à Senescência
/
Neoplasias
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article