Targeting Cathepsin C in Cancer Metastasis: Protease Network Activation, Inflammatory Crosstalk, and Therapeutic...

Cathepsin C (CTSC), also known as dipeptidyl peptidase I, is an upstream activator of serine protease networks that may promote metastatic progression through inflammatory amplification and microenvironmental remodeling. Increasing evidence suggests that CTSC contributes to cancer progression not simply as an overexpressed lysosomal protease, but as a context-dependent regulator of metastatic traits. This review summarizes the structure, maturation, and biological functions of CTSC, with emphasis on its protease-activating capacity and its links to tumor-associated inflammation. Current evidence connecting CTSC to epithelial-mesenchymal transition, extracellular matrix remodeling, neutrophil extracellular trap formation, and immune microenvironment reprogramming is then synthesized across hepatocellular carcinoma, renal cell carcinoma, breast cancer, colorectal cancer, non-small-cell lung cancer, and glioma. Available data most strongly support a pro-metastatic role for CTSC in breast cancer and colorectal cancer, whereas evidence in several other malignancies remains predominantly preclinical and mechanistically incomplete. Importantly, CTSC is better viewed as a targetable protease network hub than as a universal pan-cancer metastatic driver. The biomarker potential and therapeutic relevance of CTSC are also evaluated, with particular attention to the opportunities and limitations of current DPP-1/CTSC inhibitors and the need for tumor-specific translational strategies. Overall, CTSC represents a promising but still incompletely validated target in oncology, and future work should prioritize tissue-specific dependency, biomarker qualification, and rational combination approaches.