Integrin β4 Regulates SPARC Protein to Promote Invasion
The α6β4 integrin (referred to as “β4” 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 β4-mediated inva...
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Veröffentlicht in: | The Journal of biological chemistry 2012-03, Vol.287 (13), p.9835-9844 |
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Sprache: | eng |
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Zusammenfassung: | The α6β4 integrin (referred to as “β4” 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 β4-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 β4 integrin expression and signaling impacted SPARC expression and that SPARC facilitates β4-mediated invasion. Expression of β4 in β4-deficient cells reduced the expression of a specific microRNA (miR-29a) that targets SPARC and impedes invasion. In cells that express endogenous β4, miR-29a expression is low and β4 ligation facilitates the translation of SPARC through a TOR-dependent mechanism. The results obtained in this study demonstrate that β4 can regulate SPARC expression and that SPARC is an effector of β4-mediated invasion. They also highlight a potential role for specific miRNAs in executing the functions of integrins.
Integrin α6β4 is an adhesion receptor for the laminins that promotes carcinoma invasion.
α6β4 ligation enhances SPARC translation, and its expression can repress a miRNA that inhibits invasion and targets SPARC.
The regulation of SPARC by integrin-mediated mechanisms can facilitate invasion.
These data enhance our understanding of how α6β4 contributes to the invasive process and demonstrate integrin regulation of miRNAs. |
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ISSN: | 0021-9258 1083-351X |
DOI: | 10.1074/jbc.M111.317727 |