The Crucial Nexus: Unveiling the Role of Collagen in Cancer Progression

The complex interplay between collagen and cancer cells within the tumor microenvironment (TME) highlights the pivotal role of collagens in cancer progression, prognosis and therapy resistance. As a critical structural protein of the extracellular matrix (ECM), collagen not only maintains tissue architecture but also regulates key physiological functions through complex biosynthetic pathways. Deregulation in collagen biosynthesis, characterized by abnormal transcription, post-translational modifications, and deposition, contributes to ECM remodeling and tumor progression. This review explores the involvement of diverse collagen family members in cancer progression across multiple cancer types. Several collagen isoforms have emerged as key players in cancer progression, influencing tumor behavior and act as potential biomarkers for prognosis. Furthermore, circulating collagen fragments in blood present promising avenues for non-invasive cancer diagnosis and disease monitoring. Tumor collagen remodeling alters ECM architecture, impacting tumor-stromal interactions and fostering a microenvironment conducive to favour invasion and metastasis. Mechanistic insights reveal that collagen-induced signalling pathways are the major drivers of stemness, drug resistance, EMT, metastasis, angiogenesis and immune evasion, which collectively shape tumor cell behavior and immune infiltration dynamics. Further, targeting tumor collagen appear to be a viable and robust strategy to treat aggressive desmoplastic and metastatic cancers.