Oxidative Stress in Cells with Extra Centrosomes Drives Non-Cell-Autonomous Invasion.
Dev Cell
; 47(4): 409-424.e9, 2018 11 19.
Article
em En
| MEDLINE
| ID: mdl-30458137
ABSTRACT
Centrosomal abnormalities, in particular centrosome amplification, are recurrent features of human tumors. Enforced centrosome amplification in vivo plays a role in tumor initiation and progression. However, centrosome amplification occurs only in a subset of cancer cells, and thus, partly due to this heterogeneity, the contribution of centrosome amplification to tumors is unknown. Here, we show that supernumerary centrosomes induce a paracrine-signaling axis via the secretion of proteins, including interleukin-8 (IL-8), which leads to non-cell-autonomous invasion in 3D mammary organoids and zebrafish models. This extra centrosomes-associated secretory phenotype (ECASP) promotes invasion of human mammary cells via HER2 signaling activation. Further, we demonstrate that centrosome amplification induces an early oxidative stress response via increased NOX-generated reactive oxygen species (ROS), which in turn mediates secretion of pro-invasive factors. The discovery that cells with extra centrosomes can manipulate the surrounding cells highlights unexpected and far-reaching consequences of these abnormalities in cancer.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
/
Tipos_de_cancer
/
Outros_tipos
Base de dados:
MEDLINE
Assunto principal:
Transformação Celular Neoplásica
/
Estresse Oxidativo
/
Centrossomo
/
Mitose
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Dev Cell
Assunto da revista:
EMBRIOLOGIA
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Reino Unido