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Removal of cell surface heparan sulfate increases TACE activity and cleavage of ErbB4 receptor

Jorma A Määttä1, Kaisa Olli, Tiina Henttinen

  • 1Turku Center for Disease Modeling/Department of Cell Biology and Anatomy, University of Turku, Turku, Finland. jmaatta@utu.fi

BMC Cell Biology
|January 28, 2009
PubMed
Abstract

Insights

Cell surface heparan sulfate removal enhances tumor necrosis factor alpha converting enzyme (TACE) activity, increasing ErbB4 intracellular domain formation. This suggests a novel mechanism for tumor cell survival.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Oncology

Background:

  • Nuclear localization of the ErbB4 receptor intracellular domain promotes cell survival.
  • ErbB4 receptor nuclear localization is observed in human breast cancer.
  • Tumor necrosis factor alpha converting enzyme (TACE) initiates the proteolytic cascade for ErbB4 intracellular domain formation.

Purpose of the Study:

  • Investigate the effect of cell surface heparan sulfate on TACE activity.
  • Determine the role of heparan sulfate in ErbB4 intracellular domain formation.

Main Methods:

  • Enzymatic removal of cell surface glycosaminoglycans (heparan sulfate and chondroitin sulfate).
  • Immunodetection assays to quantify ErbB4 intracellular domain formation.
  • Direct enzyme activity analysis of TACE.

Main Results:

  • Enzymatic removal of cell surface heparan sulfate significantly amplified TACE activity.
  • Increased ErbB4 intracellular domain formation was observed following heparan sulfate removal.
  • Chondroitin sulfate removal did not affect TACE activity or ErbB4 intracellular domain formation.

Conclusions:

  • Cell surface heparan sulfate plays a novel role in regulating TACE activity.
  • Degradation of heparan sulfate in tumor tissues may enhance ErbB4 intracellular domain formation.
  • This mechanism could contribute to tumor cell survival in cancerous tissues.

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