p66Shc mediates anoikis through RhoA.
J Cell Biol
; 179(1): 23-31, 2007 Oct 08.
Article
em En
| MEDLINE
| ID: mdl-17908916
ABSTRACT
Detachment of parenchymal cells from a solid matrix switches contextual cues from survival to death during anoikis. Marked shape changes accompany detachment and are thought to trigger cell death, although a working model to explain the coordination of attachment sensation, shape change, and cell fate is elusive. The constitutive form of the adapter Shc, p52Shc, confers survival properties, whereas the longer p66Shc signals death through association with cytochrome c. We find that cells that lack p66Shc display poorly formed focal adhesions and escape anoikis. However, reexpression of p66Shc restores anoikis through a mechanism requiring focal adhesion targeting and RhoA activation but not an intact cytochrome c-binding motif. This pathway stimulates the formation of focal adhesions and stress fibers in attached cells and tension-dependent cell death upon detachment. p66Shc may thus report attachment status to the cell by imposing a tension test across candidate anchorage points, with load failure indicating detachment.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteína rhoA de Ligação ao GTP
/
Anoikis
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Proteínas Adaptadoras de Transdução de Sinal
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Matriz Extracelular
Limite:
Humans
Idioma:
En
Revista:
J Cell Biol
Ano de publicação:
2007
Tipo de documento:
Article
País de afiliação:
Estados Unidos