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Heparanase: busy at the cell surface.
- Source :
-
Trends in biochemical sciences [Trends Biochem Sci] 2009 Oct; Vol. 34 (10), pp. 511-9. Date of Electronic Publication: 2009 Sep 03. - Publication Year :
- 2009
-
Abstract
- Heparanase activity is strongly implicated in structural remodeling of the extracellular matrix, a process which can lead to invasion by tumor cells. In addition, heparanase augments signaling cascades leading to enhanced phosphorylation of selected protein kinases and increased gene transcription associated with aggressive tumor progression. This function is apparently independent of heparan sulfate and enzyme activity, and is mediated by a novel protein domain localized at the heparanase C-terminus. Moreover, the functional repertoire of heparanase is expanded by its regulation of syndecan clustering, shedding, and mitogen binding. Recent reports indicate that modified glycol-split heparin, which inhibits heparanase activity, can profoundly inhibit the progression of tumor xenografts produced by myeloma and carcinoma cells, thus moving anti-heparanase therapy closer to reality.
- Subjects :
- Animals
Cell Adhesion physiology
Endocytosis physiology
Enzyme Activation
Glucuronidase chemistry
Glucuronidase genetics
Heparin chemistry
Heparin metabolism
Heparitin Sulfate chemistry
Heparitin Sulfate metabolism
Humans
Multiple Myeloma metabolism
Multiple Myeloma therapy
Neoplasms metabolism
Receptors, Cell Surface metabolism
Structure-Activity Relationship
Substrate Specificity
Syndecan-1 metabolism
rac GTP-Binding Proteins metabolism
src-Family Kinases metabolism
Extracellular Matrix metabolism
Glucuronidase metabolism
Signal Transduction physiology
Subjects
Details
- Language :
- English
- ISSN :
- 0968-0004
- Volume :
- 34
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Trends in biochemical sciences
- Publication Type :
- Academic Journal
- Accession number :
- 19733083
- Full Text :
- https://doi.org/10.1016/j.tibs.2009.06.005