作者
Anurag Purushothaman, Douglas R Hurst, Claudio Pisano, Shuji Mizumoto, Kazuyuki Sugahara, Ralph D Sanderson
发表日期
2011/9/2
期刊
Journal of Biological Chemistry
卷号
286
期号
35
页码范围
30377-30383
出版商
Elsevier
简介
Heparanase acts as a master regulator of the aggressive tumor phenotype in part by enhancing expression of proteins known to drive tumor progression (e.g. VEGF, MMP-9, hepatocyte growth factor (HGF), and RANKL). However, the mechanism whereby this enzyme regulates gene expression remains unknown. We previously reported that elevation of heparanase levels in myeloma cells causes a dramatic reduction in the amount of syndecan-1 in the nucleus. Because syndecan-1 has heparan sulfate chains and because exogenous heparan sulfate has been shown to inhibit the activity of histone acetyltransferase (HAT) enzymes in vitro, we hypothesized that the reduction in nuclear syndecan-1 in cells expressing high levels of heparanase would result in increased HAT activity leading to stimulation of protein transcription. We found that myeloma cells or tumors expressing high levels of heparanase and low …
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A Purushothaman, DR Hurst, C Pisano, S Mizumoto… - Journal of Biological Chemistry, 2011