Extracellular matrix proteins and cell-surface integrins (ECM-Integrin)

The interaction between extracellular matrix (ECM) proteins and cell-surface integrins is a fundamental mechanism for cell adhesion, migration, and signaling. Integrins are heterodimeric transmembrane receptors composed of alpha and beta subunits that bridge the intracellular cytoskeleton with ECM ligands such as collagen, fibronectin, and laminin [1][2]. This interaction facilitates outside-in signaling, which influences cell survival, proliferation, and differentiation by activating intracellular kinase cascades [2][3]. Conversely, inside-out signaling allows the cell to regulate the binding affinity of integrins for their extracellular ligands in response to internal stimuli [2]. In pathological states, dysregulation of the ECM-integrin axis is a hallmark of cancer metastasis, where it promotes tumor cell invasion and survival in foreign microenvironments [4]. It also plays a critical role in fibrotic diseases by driving the activation of myofibroblasts and the excessive deposition of matrix components [4]. Furthermore, integrins on leukocytes and platelets are essential for inflammatory recruitment and thrombus formation, respectively [5]. Therapeutic strategies targeting this system typically involve monoclonal antibodies or small molecules that competitively inhibit the binding of ECM ligands to specific integrin heterodimers [5]. Clinical applications of these drugs include the treatment of autoimmune diseases like multiple sclerosis, inflammatory bowel disease, and cardiovascular conditions such as acute coronary syndrome [5]. Sources: [1] Hynes, R. O. (2002). Cell; [2] Takada, Y., et al. (2007). Genome Biology; [3] Humphrey, J. D., et al. (2014). Nature Reviews Molecular Cell Biology; [4] Desgrosellier, J. S., & Cheresh, D. A. (2010). Nature Reviews Cancer; [5] Ley, K., et al. (2016). Nature Reviews Drug Discovery.

Other names

ECM-integrin axisCell-matrix adhesion systemIntegrin-ligand complexCell-surface integrin receptors

Inhibition of ligand-receptor binding to prevent cell adhesion and downstream intracellular signaling pathways.