Requirement of the conserved, hydrophobic C-terminus region for the activation of heparanase
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- 作者：Ngit Shin Lai ; Siro Simizu ; Daiki Morisaki ; Makoto Muroi ; Hiroyuki Osada
- 关键词：Heparanase ; Migration ; Invasion ; Metastasis ; Tumor cells ; Heparan sulfate ; Trafficking ; Glycosylation ; Glucuronidase ; Extracellular matrix
- 刊名：Experimental Cell Research
- 出版年：2008
- 出版时间：10 September 2008
- 年：2008
- 卷：314
- 期：15
- 页码：2834-2845
- 全文大小：1365 K
文摘
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.