14-3-3τ promotes breast cancer invasion and metastasis by inhibiting RhoGDIα.
Mol Cell Biol
; 34(14): 2635-49, 2014 Jul.
Article
em En
| MEDLINE
| ID: mdl-24820414
ABSTRACT
14-3-3τ is frequently overexpressed in breast cancer; however, whether it contributes to breast cancer progression remains undetermined. Here, we identify a critical role for 14-3-3τ in promoting breast cancer metastasis, in part through binding to and inhibition of RhoGDIα, a negative regulator of Rho GTPases and a metastasis suppressor. 14-3-3τ binds Ser174-phosphorylated RhoGDIα and blocks its association with Rho GTPases, thereby promoting epidermal growth factor (EGF)-induced RhoA, Rac1, and Cdc42 activation. When 14-3-3τ is overexpressed in MCF7 breast cancer cells that express 14-3-3τ at low levels, it increases motility, reduces adhesion, and promotes metastasis in mammary fat pad xenografts. On the other hand, depletion of 14-3-3τ in MCF7 cells and in an invasive cell line, MDA-MB231, inhibits Rho GTPase activation and blocks breast cancer migration and invasion. Moreover, 14-3-3τ overexpression in human breast tumors is associated with the activation of ROCK (a Rho GTPase effector), high metastatic rate, and shorter survival, underscoring a clinically significant role for 14-3-3τ in breast cancer progression. Our work indicates that 14-3-3τ is a novel therapeutic target to prevent breast cancer metastasis.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Mama
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Proteínas rho de Ligação ao GTP
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Proteínas 14-3-3
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Inibidor alfa de Dissociação do Nucleotídeo Guanina rho
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Metástase Neoplásica
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Mol Cell Biol
Ano de publicação:
2014
Tipo de documento:
Article