Sugar tags and tumorigenesis

摘要

The fact that the cell surface and extracellular matrix (ECM) component heparin sulfate proteoglycans (HSPGs) bind to various growth factor molecules and distribute them to targeted cell locations is known for many years (Spring et al., 1994; Nakato et al., 1995; Baeg et al., 2001; Nybakken and Perrimon, 2002; Voigt et al., 2002; Fujise et al., 2003; Johnson et al., 2004; Steigemann et al., 2004).However only during the last few years the signi?cance of producing functional proteoglycans that regulate the signaling activities are gaining importance (Sarrazin et al., 2011).Proteoglycans are widespread from bacteria to humans with diverse expression patterns.Structural and functional features of proteoglycans possess immense ability to either promote or inhibit tumorigenesis.Members of HSPG family (glypicans, syndecans, and perlecans) function as co-receptors for several growth-related signaling pathways such as Wg, Hh, Dpp to mediate various processes like proliferation, di?erentiation, morphogenesis, cell-adhesion, and cell migration (Reviewed in Lin, 2004; Yan and Lin, 2009).Studies in Drosophila have shown that glypicans like Dally (Belenkaya et al., 2004; Han et al., 2004; Vuilleumier et al., 2010; Ferreira and Milán, 2015) and Dally-like (Dlp) (Gallet et al., 2008; Szuperák et al., 2011) facilitate movement of signaling molecules to regulate tissue growth.Recent research updates demonstrate the novel role of HSPGs in regulating additional signaling pathways like JAK/STAT (Zhang et al., 2013); PI3K and TOR (Ferreira and Milán, 2015) and also in cross-talk between signaling pathways (Wg and Dpp) to mediate tumorigenesis and metastasis (Freire-de-Lima, 2014; Herranz et al., 2014; H?uselmann and Borsig, 2014).These reports underscore the importance of studying the role of functional proteoglycans.