Cancer and Metastasis Reviews

, Volume 22, Issue 2–3, pp 223–236

Roles of hepatocyte growth factor (HGF) activator and HGF activator inhibitor in the pericellular activation of HGF/scatter factor

  • Hiroaki Kataoka
  • Shiro Miyata
  • Shunro Uchinokura
  • Hiroshi Itoh
Article

DOI: 10.1023/A:1023051500010

Cite this article as:
Kataoka, H., Miyata, S., Uchinokura, S. et al. Cancer Metastasis Rev (2003) 22: 223. doi:10.1023/A:1023051500010

Abstract

The activation of hepatocyte growth factor (HGF)/ scatter factor (SF) in an extracellular milieu is a critical limiting step in HGF/SF-induced signaling that is believed to have important roles in invasive growth of tumor cells and regeneration of injured tissue. This activation is caused by a proteolytic cleavage at the bond between Arg494-Val495 in the single-chain HGF/SF precursor, generating an active two-chain heterodimeric form. The HGF activator (HGFA) is a coagulation factor XII-like serine proteinase critically involved in this process in injured tissues including tumor tissues. In the past several years, the identification of endogenous HGFA inhibitors (HAIs) has provided detailed knowledge of the regulation of HGFA activity. Currently, two types of HAIs, namely HAI-1 and HAI-2, have been reported. Both are Kunitz-type serine proteinase inhibitors and inhibit not only HGFA but also other serine proteinases, such as membrane-type serine protease 1 (matriptase), plasmin, trypsin and kallikreins. HAIs are of particular interest because they are synthesized as type-I transmembrane proteins. Therefore, HAIs must have important regulatory roles in a cell surface proteolytic reaction, which has emerged as an important mechanism for the generation of biologically active proteins mediating a diverse range of cellular functions. This review is a summary and interpretation of recent data regarding the regulation of pericellular HGF/SF activation mediated by HGFA and HAIs and includes a discussion of the possible role of the type I transmembrane Kunitz-type inhibitor in pericellular proteolysis.

hepatocyte growth factor scatter factor HGF activator HGF activator inhibitor HAI-1 invasive growth 

Copyright information

© Kluwer Academic Publishers 2003

Authors and Affiliations

  • Hiroaki Kataoka
    • 1
  • Shiro Miyata
    • 1
  • Shunro Uchinokura
    • 1
  • Hiroshi Itoh
    • 1
  1. 1.Second Department of PathologyMiyazaki Medical CollegeMiyazakiJapan

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