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.
Cover legend: The cover image is based on the Research Article The variant senescence‐associated secretory phenotype induced by centrosome amplification constitutes a pathway that activates hypoxia‐inducible factor‐1α by Selwin K. Wu et al., https://doi.org/10.1111/acel.13766. Image Credit: Remi Picò
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.