Syndecan as a Messenger to Link Diabetes and Cancer

Abstract

Cell surface syndecans are membrane-anchored proteoglycans. These glycoproteins have covalently linked glycosaminoglycan side chains. They interact via their extracellular part with various growth factors, extracellular matrix components, other cell surface molecules, and proteins involved in the regulation of blood coagulation. Thus the syndecans involve in synchronized expression patterns during embryogenesis and malignant transformation. These cell-cell interactions via their extracellular matrix ligands control cell proliferation, dynamic cytoskeletal remodeling, apoptosis and gene expression.Over the last few years, it has been widely accepted that heparan sulfate proteoglycans play a role in growth control, cell spreading, cellular recognition, cellular adhesion, and signaling, possibly as co -receptors with integrins, IGF-1R and cell -cell adhesion molecules, including fi bronectin, vitronectin, laminins, and the fi brillar collagens (Bernfi eld et al., 1999;Woods, 2001;Alexopoulou et al., 2007;Beauvais and Rapraeger, 2010). In addition, all syndecans have dibasic peptide sequence adjacent to the plasma membrane. Thus, the extracellular domains of syndecans could be cleaved by extracellular proteases. Syndecan's ectodomains have been shown to regulate a multitude of biological functions in celldependent and cell-independent approaches (Li et al., 2002;Endo et al., 2003;Elenius et al., 2004). Soluble syndecans also convert the membrane-bound receptors into soluble effectors/or antagonists. The soluble ectodomains of syndecans can compete with intact syndecans for extracellular ligands (Steinfeld et al., 1996). In this review, we will discuss the general Syndecans are membrane-anchored proteoglycans and implicated in the pathogenesis of cancer progression and metastasis. Syndecans also play important roles in interacting with growth factors, extracellular matrix and other cell surface molecules such as IGF-1 receptor. In the present review, we discuss about the syndecan structure, their role in signaling with other receptors, in addition to its general biology. The emerging roles of syndecans in the pathophysiology of human diseases, especially insulin resistance, diabetes and cancer is discussed. Abstractfeatures and their conventional roles in signaling with co-receptors. Finally, we will explore the emerging roles of syndecans in the pathophysiology of human diseases, especially type 2 diabetes. SYNDECAN STRUCTUREAll the syndecans are a type 1 transmembrane proteins that are expressed in almost every cell of the body. Four members of syndecan family have been identifi ed in mammalians such as syndecan-1, 2, 3, and 4. Syndecan-1 analogs are also identifi ed in other mammals such as mouse, rat, dog, chimpanzee, guinea pig, Chinese hamster, cat and chicken. The extracellular domains of human and mouse syndecan-1 display approximately 70% sequence homology whereas the transmembrane domain and cytoplasmic domain show 96 % and 100% sequence homology, respectively. Synthesis of four syndecan core proteins are ...