Role of heparan sulfate proteoglycans in cell signaling and cancer

Abstract

Publisher Summary Heparan sulfate proteoglycans (HSPGs) are composed of a protein core modified on specific serine residues by the addition of heparan sulfate (HS) glucosaminoglycans (GAGs) synthesized in the Golgi. Three distinct types of proteins can serve as the HSPG cores: the transmembrane proteins encoded by the syndecan genes, the glycosylphosphatidylinositol (GPI) membrane-bound glypicans, and the extracellular matrix secreted perlecan proteins. The chapter presents the two major advances made in understanding the role of HSPGs in development and cancer. First, studies in Drosophila have identified many mutations in either the biosynthetic enzymes for example, Sugarless (Sgl), Sulfateless (Sfl), Tout velu (Ttv); or the protein cores for example, syndecans and glypicans. Analysis of the mutant phenotypes has revealed the critical roles of HSPGs in modulating various growth factor signaling pathways. Second, many mutations linked to human cancers have been isolated and shown to correspond to defects in the biosynthesis of HSPGs. The chapter explains the importance of HSPGs in cell signaling and provides insights into their functions. Modulating the activity of HSPGs could influence the development of cancers caused by aberrant cell signaling. The chapter concludes that HSPGs constitute important targets for therapeutics to treat some human tumors.