Kinesin-5 Contributes to Spindle-length Scaling in the Evolution of Cancer toward Metastasis.
Sci Rep
; 6: 35767, 2016 10 21.
Article
em En
| MEDLINE
| ID: mdl-27767194
ABSTRACT
During natural evolution, the spindles often scale with cell sizes to orchestrate accurate chromosome segregation. Whether in cancer evolution, when the constraints on genome integrity are relaxed, cancer cells may evolve the spindle to confer other advantages has not been investigated. Using invasion as a selective pressure in vitro, we found that a highly metastatic cancer clone displays a lengthened metaphase spindle, with faster spindle elongation that correlates with transiently elevated speed of cell migration. We found that kinesin-5 is upregulated in this malignant clone, and weak inhibition of kinesin-5 activity could revert the spindle to a smaller aspect ratio, decrease the speed of spindle pole separation, and suppress post-mitotic cell migration. A correlation was found between high aspect ratio and strong metastatic potential in cancers that evolved and were selected in vivo, implicating that the spindle aspect ratio could serve as a promising cellular biomarker for metastatic cancer clones.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Cinesinas
/
Fuso Acromático
/
Metástase Neoplásica
Limite:
Humans
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article