Cdc42 promotes transendothelial migration of cancer cells through ß1 integrin.
J Cell Biol
; 199(4): 653-68, 2012 Nov 12.
Article
en En
| MEDLINE
| ID: mdl-23148235
ABSTRACT
Cancer cells interact with endothelial cells during the process of metastatic spreading. Here, we use a small interfering RNA screen targeting Rho GTPases in cancer cells to identify Cdc42 as a critical regulator of cancer cell-endothelial cell interactions and transendothelial migration. We find that Cdc42 regulates ß1 integrin expression at the transcriptional level via the transcription factor serum response factor (SRF). ß1 integrin is the main target for Cdc42-mediating interaction of cancer cells with endothelial cells and the underlying extracellular matrix, as exogenous ß1 integrin expression was sufficient to rescue the Cdc42-silencing phenotype. We show that Cdc42 was required in vivo for cancer cell spreading and protrusion extension along blood vessels and retention in the lungs. Interestingly, transient Cdc42 depletion was sufficient to decrease experimental lung metastases, which suggests that its role in endothelial attachment is important for metastasis. By identifying ß1 integrin as a transcriptional target of Cdc42, our results provide new insight into Cdc42 function.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Integrina beta1
/
Proteína de Unión al GTP cdc42
/
Migración Transendotelial y Transepitelial
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
J Cell Biol
Año:
2012
Tipo del documento:
Article
País de afiliación:
Reino Unido