Fig. 1
From: Mechanical forces in the tumor microenvironment: roles, pathways, and therapeutic approaches
Major components of the ECM: collagen, proteoglycans, laminin, and fibronectin. (a) Collagen is synthesized in the endoplasmic reticulum and undergoes preliminary assembly into a triple-helix structure before being transported to the ECM via the Golgi apparatus. The N-propeptides (retained in type V and XI collagen) and C-propeptides are cleaved by proteases in the ECM, allowing collagen to self-assemble into collagen fibrils. (b) Proteoglycans in the ECM primarily include perlecan, hyalectans, and SLRPs. Perlecan not only cross-links with collagen to promote ECM maturation but also regulates ECM-related gene expression. Hyalectans interact with integrins and hyaluronan within the ECM, facilitating ECM remodeling. SLRPs bind to collagen and protect it from proteolytic degradation, thereby maintaining ECM structural stability. (c) Laminin consists of α, β, and γ polypeptide chains forming a trimeric structure. This laminin trimer binds to type IV collagen via HSPGs in proteoglycans, thereby contributing to matrix formation. (d) Fibronectin forms dimers through C-terminal disulfide bonds, which further assemble into fibronectin fibrils. These fibrils interact with integrins via the RGD sequence to stabilize the ECM structure