TY - JOUR
T1 - Requirement of the conserved, hydrophobic C-terminus region for the activation of heparanase
AU - Lai, Ngit Shin
AU - Simizu, Siro
AU - Morisaki, Daiki
AU - Muroi, Makoto
AU - Osada, Hiroyuki
PY - 2008/9/10
Y1 - 2008/9/10
N2 - 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.
AB - 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.
KW - Extracellular matrix
KW - Glucuronidase
KW - Glycosylation
KW - Heparan sulfate
KW - Heparanase
KW - Invasion
KW - Metastasis
KW - Migration
KW - Trafficking
KW - Tumor cells
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U2 - 10.1016/j.yexcr.2008.07.004
DO - 10.1016/j.yexcr.2008.07.004
M3 - Article
C2 - 18662687
AN - SCOPUS:50049112962
VL - 314
SP - 2834
EP - 2845
JO - Experimental Cell Research
JF - Experimental Cell Research
SN - 0014-4827
IS - 15
ER -