ADAM9 in tumor biology: molecular functions, clinical implications, and therapeutic targeting

A disintegrin and metalloproteinase 9 (ADAM9), a member of the ADAM family, is expressed across multiple organs and is crucial to multiple physiological processes. Increasing evidence implicates ADAM9 in cancer progression through extracellular matrix (ECM) remodeling, protein shedding, and tumor microenvironment modulation. This study comprehensively reviews the literature on the clinical significance of ADAM9 and the mechanistic roles of ADAM9 in cancer. The results of our pan-cancer analysis demonstrated that ADAM9 is frequently upregulated and consistently associated with poor prognosis across tumor types. The results of in silico analyses also revealed that increased ADAM9 expression is correlated with an immunosuppressive tumor microenvironment and the activation of cancer-promoting pathways, such as cell cycle progression, epithelial-mesenchymal transition (EMT), and metabolism. This study also reviewed therapeutic strategies targeting ADAM9 and evaluated their potential in cancer treatment. This review provides insights into ADAM9 as both a biomarker of malignancy and a promising therapeutic target.