The multifaceted roles of MCAM in development, homeostasis, pathological conditions, and cancer

MCAM (melanoma cell adhesion molecule), identified in human melanoma in 1987, has garnered attention due to its diverse roles in development, homeostasis, and various diseases, including cancer. Initially recognized for its differential expression in tumors, MCAM plays a crucial role in cell adhesion, migration, and signaling. It acts as a receptor for multiple ligands, impacting angiogenesis, inflammation, and immune responses. MCAM is expressed in developing embryos and is implicated in trophoblast invasion during implantation, serving as a marker for placental health. In adults, MCAM is predominantly found in the vascular system and modulates endothelium homeostasis and inflammatory processes. Moreover, its involvement in cancer is marked by associations with tumor progression, particularly through epithelial-mesenchymal transition (EMT) pathways, highlighting its potential as a prognostic biomarker. Elevated levels of soluble MCAM have been linked to poor outcomes in various malignancies and can influence tumor microenvironments. This review synthesizes current understanding of MCAM's multifunctional roles, its bidirectional influence in health and disease, and its potential as a therapeutic target in cancer.