Integrin ß4 regulates SPARC protein to promote invasion.
J Biol Chem
; 287(13): 9835-9844, 2012 Mar 23.
Article
en En
| MEDLINE
| ID: mdl-22308039
The α6ß4 integrin (referred to as "ß4" integrin) is a receptor for laminins that promotes carcinoma invasion through its ability to regulate key signaling pathways and cytoskeletal dynamics. An analysis of published Affymetrix GeneChip data to detect downstream effectors involved in ß4-mediated invasion of breast carcinoma cells identified SPARC, or secreted protein acidic and rich in cysteine. This glycoprotein has been shown to play an important role in matrix remodeling and invasion. Our analysis revealed that manipulation of ß4 integrin expression and signaling impacted SPARC expression and that SPARC facilitates ß4-mediated invasion. Expression of ß4 in ß4-deficient cells reduced the expression of a specific microRNA (miR-29a) that targets SPARC and impedes invasion. In cells that express endogenous ß4, miR-29a expression is low and ß4 ligation facilitates the translation of SPARC through a TOR-dependent mechanism. The results obtained in this study demonstrate that ß4 can regulate SPARC expression and that SPARC is an effector of ß4-mediated invasion. They also highlight a potential role for specific miRNAs in executing the functions of integrins.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Biosíntesis de Proteínas
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Regulación Neoplásica de la Expresión Génica
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Osteonectina
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Integrina beta4
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Proteínas de Neoplasias
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Neoplasias
Límite:
Humans
Idioma:
En
Revista:
J Biol Chem
Año:
2012
Tipo del documento:
Article
Pais de publicación:
Estados Unidos