Role of the polarity determinant crumbs in suppressing mammalian epithelial tumor progression.
Cancer Res
; 68(11): 4105-15, 2008 Jun 01.
Article
em En
| MEDLINE
| ID: mdl-18519669
ABSTRACT
Most tumors are epithelial-derived, and although disruption of polarity and aberrant cellular junction formation is a poor prognosticator in human cancer, the role of polarity determinants in oncogenesis is poorly understood. Using in vivo selection, we identified a mammalian orthologue of the Drosophila polarity regulator crumbs as a gene whose loss of expression promotes tumor progression. Immortal baby mouse kidney epithelial cells selected in vivo to acquire tumorigenicity displayed dramatic repression of crumbs3 (crb3) expression associated with disruption of tight junction formation, apicobasal polarity, and contact-inhibited growth. Restoration of crb3 expression restored junctions, polarity, and contact inhibition while suppressing migration and metastasis. These findings suggest a role for mammalian polarity determinants in suppressing tumorigenesis that may be analogous to the well-studied polarity tumor suppressor mechanisms in Drosophila.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Epiteliais e Glandulares
/
Junções Íntimas
/
Proteínas de Membrana
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Cancer Res
Ano de publicação:
2008
Tipo de documento:
Article
País de afiliação:
Estados Unidos