MUC16

MUC16, also known as mucin 16 or CA125, is a high molecular weight cell-surface mucin expressed by secretory epithelia, most prominently the ovarian surface epithelium. The protein is large and features an extracellular N-terminal domain containing many tandem repeats that are rich in O-glycosylation, followed by a single transmembrane region and a short cytoplasmic tail. The extracellular portion is cleaved and shed into body fluids, giving rise to the CA125 antigen measured in serum.

Physiological roles of MUC16 include forming a protective mucus barrier, contributing to lubrication, and modulating cell–cell and cell–matrix interactions at epithelial surfaces. The mucin can also influence immune recognition by masking underlying cell-surface antigens, aiding resilience against environmental stress.

In cancer, MUC16 is frequently overexpressed, most notably in ovarian cancer, where serum CA125 is used to monitor disease course. CA125 testing is not a definitive screening tool due to limited sensitivity and specificity, and elevated levels can occur in benign conditions and other malignancies. MUC16 also engages in adhesion through interaction with mesothelin on mesothelial cells, a binding implicated in tumor cell attachment and potential peritoneal metastasis. Beyond diagnostics, MUC16 has attracted interest as a therapeutic target, with research into vaccines and antibody- or cell-based approaches aimed at targeting the protein, though clinical benefits require further validation.

Overall, MUC16 is a large, cell-surface mucin with a prominent role in barrier function and cell signaling, and it serves as a clinically important biomarker and investigational target in oncology.