Title

Integrin beta4 regulates SPARC protein to promote invasion

UMMS Affiliation

Department of Cancer Biology

Date

3-23-2012

Document Type

Article

Subjects

Cell Line, Tumor; *Gene Expression Regulation, Neoplastic; Humans; Integrin beta4; MicroRNAs; Neoplasm Invasiveness; Neoplasm Proteins; Neoplasms; Osteonectin; *Protein Biosynthesis

Abstract

The alpha6beta4 integrin (referred to as "beta4" 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 beta4-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 beta4 integrin expression and signaling impacted SPARC expression and that SPARC facilitates beta4-mediated invasion. Expression of beta4 in beta4-deficient cells reduced the expression of a specific microRNA (miR-29a) that targets SPARC and impedes invasion. In cells that express endogenous beta4, miR-29a expression is low and beta4 ligation facilitates the translation of SPARC through a TOR-dependent mechanism. The results obtained in this study demonstrate that beta4 can regulate SPARC expression and that SPARC is an effector of beta4-mediated invasion. They also highlight a potential role for specific miRNAs in executing the functions of integrins.

Comments

Citation: J Biol Chem. 2012 Mar 23;287(13):9835-44. Epub 2012 Feb 3. Link to article on publisher's site

Co-author Kristen Gerson is a student in the Cancer Biology and MD/PhD programs in the Graduate School of Biomedical Sciences (GSBS) at UMass Medical School. Jeffrey Shearstone is also a student in the Cancer Biology program.

Related Resources

Link to Article in PubMed

PubMed ID

22308039