| Heparanase regulates levels of syndecan-1 in the nucleus. | |
| | |
MedLine Citation:
|
PMID: 19305494 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Syndecan-1 is a transmembrane heparan sulfate-bearing proteoglycan known to regulate multiple biological functions at the cell surface and within the extracellular matrix. Its functional activity can be modulated by heparanase, an enzyme that cleaves heparan sulfate chains and whose expression has been associated with an aggressive phenotype in many cancers. In addition to remodeling syndecan-1 by cleaving its heparan sulfate chains, heparanase influences syndecan-1 location by upregulating expression of enzymes that accelerate its shedding from the cell surface. In the present study we discovered that heparanase also alters the level of nuclear syndecan-1. Upon upregulation of heparanase expression or following addition of recombinant heparanase to myeloma cells, the nuclear localization of syndecan-1 drops dramatically as revealed by confocal microscopy, western blotting and quantification by ELISA. This effect requires enzymatically active heparanase because cells expressing high levels of mutated, enzymatically inactive heparanase, failed to diminish syndecan-1 levels in the nucleus. Although heparan sulfate function within the nucleus is not well understood, there is emerging evidence that it may act to repress transcriptional activity. The resulting changes in gene expression facilitated by the loss of nuclear syndecan-1 could explain how heparanase enhances expression of MMP-9, VEGF, tissue factor and perhaps other effectors that condition the tumor microenvironment to promote an aggressive cancer phenotype. |
| | |
Authors:
|
Ligong Chen; Ralph D Sanderson |
Related Documents
:
|
8680484 - The roles of tissue inhibitors of metalloproteinases in tissue remodelling and cell gro... 21431734 - Localization and anchorage of maternal mrnas to cortical structures of ascidian eggs an... 14718544 - Membrane-type 1 matrix metalloproteinase cytoplasmic tail-binding protein-1 is a new me... 9933484 - Expression of gelatinase a and its activator mt1-mmp in the inflammatory periprosthetic... 12520524 - Vitamin d and bone. 11500464 - In vivo and in vitro studies of cytosolic phospholipase a2 expression in helicobacter p... |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural Date: 2009-03-23 |
Journal Detail:
|
Title: PloS one Volume: 4 ISSN: 1932-6203 ISO Abbreviation: PLoS ONE Publication Date: 2009 |
Date Detail:
|
Created Date: 2009-03-23 Completed Date: 2009-04-24 Revised Date: 2009-11-18 |
Medline Journal Info:
|
Nlm Unique ID: 101285081 Medline TA: PLoS One Country: United States |
Other Details:
|
Languages: eng Pagination: e4947 Citation Subset: IM |
Affiliation:
|
Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Cell Line, Tumor Cell Nucleus / metabolism* Gene Expression Regulation Glucuronidase / genetics, metabolism* Humans Recombinant Proteins / genetics, metabolism Syndecan-1 / genetics, metabolism* |
| Grant Support | |
ID/Acronym/Agency:
|
CA013148/CA/NCI NIH HHS; CA103054/CA/NCI NIH HHS; CA135075/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Recombinant Proteins; 0/Syndecan-1; EC 3.2.1.-/heparanase; EC 3.2.1.31/Glucuronidase |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Alveolar epithelial type II cells activate alveolar macrophages and mitigate P. Aeruginosa infection...
Next Document: Enzymatic primer-extension with glycerol-nucleoside triphosphates on DNA templates.