Ilona Kovalszky1, Anders Hjerpe2, Katalin Dobra3. 1. First Department of Pathology & Experimental Cancer Research Semmelweis University, Üllői street 26, Budapest 1085, Hungary. 2. Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital F46, SE-141 86 Stockholm Sweden. 3. Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital F46, SE-141 86 Stockholm Sweden. Electronic address: katalin.dobra@ki.se.
Abstract
BACKGROUND: Heparan sulfate proteoglycans (HSPGs) are important constituents of the cell membrane and they act as co-receptors for cellular signaling. Syndecan-1, glypican and perlecan also translocate to the nucleus in a regulated manner. Similar nuclear transport of growth factors and heparanase indicate a possible co-regulation and functional significance. SCOPE OF REVIEW: In this review we dissect the structural requirement for the nuclear translocation of HSPGs and their functional implications.s MAJOR CONCLUSIONS: The functions of the nuclear HSPGs are still incompletely understood. Evidence point to possible functions in hampering cell proliferation, inhibition of DNA topoisomerase I activity and inhibition of gene transcription. GENERAL SIGNIFICANCE: HSPGs influence the behavior of malignant tumors in many different ways. Modulating their functions may offer powerful tools to control fundamental biological processes and provide the basis for subsequent targeted therapies in cancer. This article is part of a Special Issue entitled Matrix-mediated cell behaviour and properties.
BACKGROUND: Heparan sulfate proteoglycans (HSPGs) are important constituents of the cell membrane and they act as co-receptors for cellular signaling. Syndecan-1, glypican and perlecan also translocate to the nucleus in a regulated manner. Similar nuclear transport of growth factors and heparanase indicate a possible co-regulation and functional significance. SCOPE OF REVIEW: In this review we dissect the structural requirement for the nuclear translocation of HSPGs and their functional implications.s MAJOR CONCLUSIONS: The functions of the nuclear HSPGs are still incompletely understood. Evidence point to possible functions in hampering cell proliferation, inhibition of DNA topoisomerase I activity and inhibition of gene transcription. GENERAL SIGNIFICANCE: HSPGs influence the behavior of malignant tumors in many different ways. Modulating their functions may offer powerful tools to control fundamental biological processes and provide the basis for subsequent targeted therapies in cancer. This article is part of a Special Issue entitled Matrix-mediated cell behaviour and properties.
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