Requirement of the conserved, hydrophobic C-terminus region for the activation of heparanase

Ngit Shin Lai, Siro Simizu, Daiki Morisaki, Makoto Muroi, Hiroyuki Osada

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Heparanase is an endo-β-d-glucuronidase responsible for the cleavage of heparan sulfate, participating in extracellular matrix degradation and remodeling. Heparanase activity is well correlated with the potential for metastasis and angiogenesis in a large number of tumor-derived cell types, directly implicating the involvement of heparanase in tumor progression. Here, we provide the first evidence that the hydrophobic C-terminus region of heparanase has specific roles in intracellular trafficking, secretion, activation, and heparanase-mediated tumor cell migration. Furthermore, partial deletion of this hydrophobic C-terminus region, substitution within the hydrophobic C-terminus region to hydrophilic amino acids, and experiments of single amino acid mutations further point out the importance of the hydrophobic C-terminus region. Therefore, our findings suggest that the hydrophobic C-terminus region of heparanase is a determinant for its intracellular trafficking to the Golgi apparatus, followed by secretion, activation, and tumor cell migration.

Original languageEnglish
Pages (from-to)2834-2845
Number of pages12
JournalExperimental Cell Research
Volume314
Issue number15
DOIs
Publication statusPublished - 2008 Sep 10
Externally publishedYes

Keywords

  • Extracellular matrix
  • Glucuronidase
  • Glycosylation
  • Heparan sulfate
  • Heparanase
  • Invasion
  • Metastasis
  • Migration
  • Trafficking
  • Tumor cells

ASJC Scopus subject areas

  • Cell Biology

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