Cancer and Metastasis Reviews

, Volume 22, Issue 2, pp 237–258

Membrane anchored serine proteases: A rapidly expanding group of cell surface proteolytic enzymes with potential roles in cancer

  • Sarah Netzel-Arnett
  • John D. Hooper
  • Roman Szabo
  • Edwin L. Madison
  • James P. Quigley
  • Thomas H. Bugge
  • Toni M. Antalis
Article

DOI: 10.1023/A:1023003616848

Cite this article as:
Netzel-Arnett, S., Hooper, J.D., Szabo, R. et al. Cancer Metastasis Rev (2003) 22: 237. doi:10.1023/A:1023003616848

Abstract

Dysregulated proteolysis is a hallmark of cancer. Malignant cells require a range of proteolytic activities to enable growth, survival, and expansion. Serine proteases of the S1 or trypsin-like family have well recognized roles in the maintenance of normal homeostasis as well as in the pathology of diseases such as cancer. Recently a rapidly expanding subgroup of S1 proteases has been recognized that are directly anchored to plasma membranes. These membrane anchored serine proteases are anchored either via a carboxy-terminal transmembrane domain (Type I), a carboxy terminal hydrophobic region that functions as a signal for membrane attachment via a glycosyl-phosphatidylinositol linkage (GPI-anchored), or via an amino terminal proximal transmembrane domain (Type II or TTSP). The TTSPs also encode multiple domains in their stem regions that may function in regulatory interactions. The serine protease catalytic domains of these enzymes show high homology but also possess features indicating unique substrate specificities. It is likely that the membrane anchored serine proteases have evolved to perform complex functions in the regulation of cellular signaling events at the plasma membrane and within the extracellular matrix. Disruption or mutation of several of the genes encoding these proteases are associated with disease. Many of the membrane anchored serine proteases show restricted tissue distribution in normal cells, but their expression is widely dysregulated during tumor growth and progression. Diagnostic or therapeutic targeting of the membrane anchored serine proteases has potential as promising new approaches for the treatment of cancer and other diseases.

serine proteasecancertransmembraneGPI anchorTTSPmembrane

Copyright information

© Kluwer Academic Publishers 2003

Authors and Affiliations

  • Sarah Netzel-Arnett
    • 1
  • John D. Hooper
    • 2
  • Roman Szabo
    • 3
  • Edwin L. Madison
    • 4
  • James P. Quigley
    • 2
  • Thomas H. Bugge
    • 3
  • Toni M. Antalis
    • 4
  1. 1.Vascular Biology Department, Jerome H. Holland Laboratory for the Biological SciencesAmerican Red CrossRockvilleUSA
  2. 2.Department of Cell BiologyThe Scripps Research InstituteLa JollaUSA
  3. 3.Proteases and Tissue Remodeling Unit, Oral and Pharyngeal Cancer BranchNational Institute of Dental and Craniofacial Research, National Institutes of HealthBethesdaUSA
  4. 4.Department of Molecular BiologyCorvas InternationalSan DiegoUSA