Integrin ?4 regulates SPARC protein to promote invasion.

ABSTRACT: The ?6?4 integrin (referred to as "?4" 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 ?4-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 ?4 integrin expression and signaling impacted SPARC expression and that SPARC facilitates ?4-mediated invasion. Expression of ?4 in ?4-deficient cells reduced the expression of a specific microRNA (miR-29a) that targets SPARC and impedes invasion. In cells that express endogenous ?4, miR-29a expression is low and ?4 ligation facilitates the translation of SPARC through a TOR-dependent mechanism. The results obtained in this study demonstrate that ?4 can regulate SPARC expression and that SPARC is an effector of ?4-mediated invasion. They also highlight a potential role for specific miRNAs in executing the functions of integrins.

SUBMITTER: Gerson KD 

PROVIDER: S-EPMC3323016 | biostudies-literature | 2012 Mar

REPOSITORIES: biostudies-literature