Integrins and Heparan sulfate proteoglycans

Integrins are a family of heterodimeric transmembrane receptors composed of α and β subunits that mediate adhesion between cells and the extracellular matrix (ECM), transmitting mechanical and chemical signals essential for migration, proliferation, and survival[1]. Heparan sulfate proteoglycans (HSPGs) are glycoproteins present on the cell surface and in the ECM; they consist of core proteins (such as syndecans or glypicans) carrying linear heparan sulfate glycosaminoglycan chains[1][3][5]. HSPGs typically act as low-affinity coreceptors, facilitating or modulating ligand binding to canonical signal receptors—including integrins—by clustering, scaffolding, and influencing signaling cascades[2][5]. The physical and functional interplay between integrins and HSPGs is a key determinant of cell adhesion, migration, growth factor presentation, and downstream signaling in development and disease, particularly cancer[1][2][4]. Because this entry is a combination of two distinct molecular families rather than a single entity, it is not a canonical therapeutic target; instead, therapeutic strategies may focus separately or synergistically on each class to modulate cell-ECM interactions in disease contexts[1][5].

Inhibition of integrin-ligand binding disrupts cell adhesion, migration, and angiogenesis Inhibition/modulation of heparan sulfate chain interactions can block growth factor signaling and tumor invasion