α5β1

Integrin α5β1, a heterodimer of α5 and β1 subunits, serves as a primary receptor for fibronectin and mediates cell adhesion, migration, and mechanotransduction^[1][2][3]. Mechanistically, α5β1 engagement with fibronectin triggers RhoA/ROCK/myosin-II and Arp2/3 signaling, promoting integrin clustering, focal adhesion formation, and extracellular matrix remodeling^[4][5]. In disease models, α5β1 overexpression contributes to cancer progression, including tension-dependent mammary epithelial invasion, angiogenesis, and metastasis in colorectal, cervical, and glioma models^{[6][7][8][1][9]}. Pulmonary arterial hypertension models also implicate α5β1 in vascular remodeling and pro-proliferative phenotypes, where blockade mitigates vessel obstruction and improves right ventricular function^[10][11]. Compared with related integrins, α5β1 uniquely mediates fibronectin synergy site adhesion, mechanotransduction, and autophagy initiation via FbaA pathogen recognition, distinguishing it from αv-class integrins that primarily compete during initial adhesion phases^[12][4]. Specific agonists or inhibitors, such as RGD peptides, SNAKA51 antibodies, and bispecific α5β1/αv inhibitors, allow targeted modulation of α5β1 functions for experimental and therapeutic applications^[13][14][15]. These tools enhance fibronectin matrix assembly, regulate mechanotransduction pathways, and provide preclinical strategies for controlling tumor aggressiveness, vascular remodeling, or immune-mediated clearance^[16][14][15].