Cellular Integrins and Extracellular Matrix Components (Integrin-ECM Axis)

Cellular integrins and extracellular matrix (ECM) components constitute a fundamental signaling and structural axis that governs cell-environment interactions. Integrins are heterodimeric transmembrane receptors, comprising alpha and beta subunits, that physically link the intracellular cytoskeleton to ECM ligands such as fibronectin, laminin, and collagen [1, 2]. This interaction facilitates bidirectional signaling, known as "inside-out" and "outside-in" signaling, which is essential for cell adhesion, migration, and survival [1]. In many diseases, including cancer and fibrosis, the integrin-ECM axis is hijacked, leading to enhanced tumor invasion, epithelial-mesenchymal transition, and excessive tissue scarring [4]. Consequently, this system has become a major focus for therapeutic intervention, with drugs like natalizumab and vedolizumab targeting specific integrins to treat autoimmune and inflammatory conditions [3]. However, the broad expression and functional redundancy of these molecules present significant challenges in achieving high therapeutic indices without systemic toxicity [3]. [1] Hynes, R. O. (2002). Integrins: Bidirectional, Allosteric Signaling Machines. Cell. [2] Frantz, C., et al. (2010). The extracellular matrix at a glance. Journal of Cell Science. [3] Ley, K., et al. (2016). Integrin-based therapeutics: biological basis, clinical use and new drugs. Nature Reviews Drug Discovery. [4] Hamidi, H., & Ivaska, J. (2018). Every step of the way: integrins in cancer progression and metastasis. Nature Reviews Cancer.

Other names

Cell-matrix adhesion systemIntegrin-ligand complexECM-integrin signaling pathwayCell-adhesion molecules

Inhibition of ligand binding to integrin receptors, blocking cell-ECM adhesion and downstream signaling pathways such as FAK and Src kinases.