Plasminogen activator inhibitor 1--insulin-like growth factor binding protein 3 cascade regulates stress-induced senescence.
Proc Natl Acad Sci U S A
; 109(30): 12052-7, 2012 Jul 24.
Article
em En
| MEDLINE
| ID: mdl-22778398
ABSTRACT
Cellular senescence is widely believed to play a key role in tumor suppression, but the molecular pathways that regulate senescence are only incompletely understood. By using a secretome proteomics approach, we identified insulin-like growth factor binding protein 3 (IGFBP3) as a secreted mediator of breast cancer senescence upon chemotherapeutic drug treatment. The senescence-inducing activity of IGFBP3 is inhibited by tissue-type plasminogen activator-mediated proteolysis, which is counteracted by plasminogen activator inhibitor 1 (PAI-1), another secreted mediator of senescence. We demonstrate that IGFBP3 is a critical downstream target of PAI-1-induced senescence. These results suggest a role for an extracellular cascade of secreted proteins in the regulation of cellular senescence.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Estresse Fisiológico
/
Senescência Celular
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Ativador de Plasminogênio Tecidual
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Inibidor 1 de Ativador de Plasminogênio
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Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina
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Proteólise
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Neoplasias
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article