Type I collagen matrix signaling in cancer: receptor sensing and mechanotransduction.

Type I collagen is a major fibrillar component of the tumor extracellular matrix (ECM) and functions as a dynamic extracellular signaling platform. Its biological output is shaped by the type I collagen matrix state, comprising collagen abundance, trimeric composition, post-translational modifications, cross-linking, fibrillar organization and alignment, proteolytic turnover, cellular origin, and spatial distribution. This collagen-specific state is one component of the broader ECM state and regulates tissue mechanics, ligand accessibility, cell-matrix force transmission, vascular perfusion, and immune-cell positioning. In collagen-rich tumors, collagen-binding receptors, including integrins, discoidin domain receptors 1/2 (DDR1/DDR2), and leukocyte-associated immunoglobulin-like receptor 1 (LAIR1), function as proximal sensors of collagen ligands. Together with Piezo1-mediated mechanosensing and mechanochemical signaling involving transforming growth factor-β (TGF-β)/SMAD and RhoA/ROCK-YAP/TAZ, these receptor systems translate collagen composition, architecture, and mechanics into adhesion, migration, epithelial-mesenchymal plasticity, mechanoadaptation, immune suppression, and therapeutic resistance. These responses vary with tumor type, disease stage, cancer-associated fibroblast states, immune composition, and organ microenvironment. This review integrates type I collagen matrix formation, maturation, state-dependent receptor engagement, mechanotransduction, tissue-level consequences, and therapeutic targeting. Multidimensional assessment of pathological type I collagen matrix states may guide matrix normalization and receptor-selective therapeutic strategies.