COL10A1 at the crossroads of tumor signaling networks and environment remodeling

Collagen type X, encoded by COL10A1 and physiologically expressed predominantly by hypertrophic chondrocytes during endochondral ossification, is aberrantly abundant in diverse solid tumors and is increasingly associated with aggressive disease and adverse clinical outcomes. However, its oncological significance remains difficult to interpret because its cellular origin is frequently unresolved. In this review, we synthesize evidence across cancer types using a source-conditioned framework, especially distinguishing collagen X derived from cancer-associated fibroblasts (CAFs), tumor cells or unresolved mixtures of both. We examine how producer-cell identity may influence extracellular localization, signaling pathways interactions and responses in recipient cells. We discuss its involvement in key oncogenic signaling axes, including extracellular-matrix organization, epithelial-to-mesenchymal transition, invasion, metastasis and immune remodeling, including the TGF-β1(Transforming Growth Factor β1)/SOX9 loop in gastric cancer and the DDR2/FAK pathway in lung adenocarcinoma. Although tissue COL10A1 expression and circulating collagen X show potential as diagnostic and prognostic biomarkers, evidence for treatment prediction remains limited, and direct pharmacological engagement of collagen X has not been established. Resolving its cellular source, receptor dependence and spatial context will be essential for determining whether COL10A1 represents a biomarker, a context-specific tumor dependency or a tractable therapeutic target.