Integrin-linked protein kinase regulates fibronectin matrix assembly, E-cadherin expression, and tumorigenicity.
J Biol Chem
; 273(1): 528-36, 1998 Jan 02.
Article
em En
| MEDLINE
| ID: mdl-9417112
ABSTRACT
Fibronectin (Fn) matrix plays important roles in many biological processes including morphogenesis and tumorigenesis. Recent studies have demonstrated a critical role of integrin cytoplasmic domains in regulating Fn matrix assembly, implying that intracellular integrin-binding proteins may be involved in controlling extracellular Fn matrix assembly. We report here that overexpression of integrin-linked kinase (ILK), a newly identified serine/threonine kinase that binds to the integrin beta1 cytoplasmic domain, dramatically stimulated Fn matrix assembly in epithelial cells. The integrin-linked kinase activity is involved in transducing signals leading to the up-regulation of Fn matrix assembly, as overexpression of a kinase-inactive ILK mutant failed to enhance the matrix assembly. Moreover, the increase in Fn matrix assembly induced by ILK overexpression was accompanied by a substantial reduction in the cellular E-cadherin. Finally, we show that ILK-overexpressing epithelial cells readily formed tumors in nude mice, despite forming an extensive Fn matrix. These results identify ILK as an important regulator of pericellular Fn matrix assembly, and suggest a novel critical role of this integrin-linked kinase in cell growth, cell survival, and tumorigenesis.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Quinases
/
Caderinas
/
Transformação Celular Neoplásica
/
Integrina beta1
/
Matriz Extracelular
Limite:
Animals
Idioma:
En
Ano de publicação:
1998
Tipo de documento:
Article