ITGA1

Integrin alpha-1 (ITGA1), also known as CD49a or VLA-1, is a transmembrane receptor that heterodimerizes with β1 integrin (ITGB1) to form the collagen/laminin-binding receptor α1β1. This integrin facilitates cell adhesion to extracellular matrix (ECM) components, primarily collagens IV and VI, and laminins, mediating bidirectional signaling critical for cell migration, proliferation, and tissue remodeling. ITGA1 activates intracellular pathways such as FAK/PI3K/Akt and MAPK cascades, regulating cellular responses to mechanical cues and ECM stiffness. It is highly expressed in activated fibroblasts, smooth muscle cells, and certain epithelial lineages, where it modulates interactions between stromal and parenchymal tissues during development and repair.
Dysregulation of ITGA1 is implicated in fibrotic disorders (e.g., pulmonary and hepatic fibrosis), tumor progression, and chronic inflammatory diseases. Its overexpression in cancer-associated fibroblasts promotes ECM deposition and metastatic niche formation in carcinomas. Therapeutic targeting remains exploratory, with preclinical studies evaluating monoclonal antibodies (e.g., MNAC13) and small-molecule inhibitors against ITGA1’s ligand-binding domain. Recent phase I trials for idiopathic pulmonary fibrosis have tested antisense oligonucleotides to disrupt ITGA1-mediated profibrotic signaling, showing modest efficacy in reducing collagen deposition. Dual-targeting strategies combining ITGA1 inhibition with immune checkpoint blockers are under investigation for solid tumors.