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Quantitative Measurement of Invadopodia-mediated Extracellular Matrix Proteolysis in Single and Multicellular Contexts
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Published on: August 27, 2012

Integrin β4 regulates SPARC protein to promote invasion

Kristin D Gerson1, Jeffrey R Shearstone1, V S R Krishna Maddula2

  • 1Department of Cancer Biology, University of Massachusetts Medical School, Worcester, Massachusetts 01605 and.

The Journal of Biological Chemistry
|February 7, 2012
PubMed

Insights

The α6β4 integrin promotes carcinoma invasion by regulating SPARC expression. This involves microRNA-29a and a TOR-dependent mechanism, highlighting integrins

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Oncology

Background:

  • The α6β4 integrin (β4) is a laminin receptor crucial for carcinoma invasion.
  • It influences signaling pathways and cytoskeletal dynamics.
  • SPARC (secreted protein acidic and rich in cysteine) is implicated in matrix remodeling and invasion.

Purpose of the Study:

  • To identify downstream effectors of β4-mediated breast carcinoma cell invasion.
  • To elucidate the regulatory relationship between β4 integrin and SPARC.
  • To investigate the role of microRNAs in this process.

Main Methods:

  • Analysis of Affymetrix GeneChip data.
  • Manipulation of β4 integrin expression and signaling.
  • Assessment of SPARC and microRNA (miR-29a) expression levels.
  • Investigation of TOR-dependent translation.

Main Results:

  • SPARC was identified as a downstream effector of β4-mediated invasion.
  • β4 integrin expression inversely correlated with miR-29a levels.
  • β4 ligation enhanced SPARC translation via a TOR-dependent pathway.
  • SPARC was confirmed to facilitate β4-mediated invasion.

Conclusions:

  • β4 integrin regulates SPARC expression and facilitates carcinoma invasion.
  • miR-29a acts as a suppressor of SPARC and invasion.
  • Integrin functions may be executed through microRNA regulation.

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