RasGRF suppresses Cdc42-mediated tumour cell movement, cytoskeletal dynamics and transformation.
Nat Cell Biol
; 13(7): 819-26, 2011 Jun 19.
Article
em En
| MEDLINE
| ID: mdl-21685891
ABSTRACT
Individual tumour cells move in three-dimensional environments with either a rounded or an elongated 'mesenchymal' morphology. These two modes of movement are tightly regulated by Rho family GTPases elongated movement requires activation of Rac1, whereas rounded/amoeboid movement engages specific Cdc42 and Rho signalling pathways. In siRNA screens targeting the genes encoding guanine nucleotide exchange factors (GEFs), we found that the Ras GEF RasGRF2 regulates conversion between elongated- and rounded-type movement. RasGRF2 suppresses rounded movement by inhibiting the activation of Cdc42 independently of its capacity to activate Ras. RasGRF2 and RasGRF1 directly bind to Cdc42, outcompeting Cdc42 GEFs, thereby preventing Cdc42 activation. By this mechanism, RasGRFs regulate other Cdc42-mediated cellular processes such as the formation of actin spikes, transformation and invasion in vitro and in vivo. These results demonstrate a role for RasGRF GEFs as negative regulators of Cdc42 activation.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Citoesqueleto
/
Movimento Celular
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Transformação Celular Neoplásica
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Proteína cdc42 de Ligação ao GTP
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Fatores ras de Troca de Nucleotídeo Guanina
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Forma Celular
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Melanoma
Limite:
Animals
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Humans
Idioma:
En
Revista:
Nat Cell Biol
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Espanha