Collagen remodeling-mediated signaling pathways and their impact on tumor therapy

In addition to their traditional roles in maintaining tissue morphology and organ development, emerging evidence suggests that collagen (COL) remodeling-referring to dynamic changes in the quantity, stiffness, arrangements, cleavage states, and homo-/hetero-trimerization of COLs-serves as a key signaling mechanism that governs tumor growth and metastasis. COL receptors act as switches, linking various forms of COL remodeling to different cell types during cancer progression, including cancer cells, immune cells, and cancer-associated fibroblasts. In this review, we summarize recent findings on the signaling pathways mediated by COL arrangement, cleavage, and trimerization states (both homo- and hetero-), as well as the roles of the primary COL receptors-integrin, DDR1/2, LAIR-1/2, MRC2, and GPVI-in cancer progression. We also discuss the latest therapeutic strategies targeting COL fragments, cancer-associated fibroblasts, and COL receptors, including integrins, DDR1/2, and LAIR1/2. Understanding the pathways modulated by COL remodeling and COL receptors in various pathological contexts will pave the way for developing new precision therapies.