Mucin 16 ectodomain (MUC16 ectodomain)

Mucin 16 ectodomain refers to the membrane-proximal extracellular portion of the Mucin 16 (MUC16) protein, a large transmembrane glycoprotein predominantly expressed on the apical surface of epithelial cells in reproductive, respiratory, and ocular tissues[1][2][3]. MUC16 is best known as the precursor of the CA125 antigen, a widely used biomarker for ovarian cancer, but its membrane-proximal ectodomain is structurally distinct from the tandem repeat region that encodes CA125[1]. This ectodomain includes a juxtamembrane segment comprising approximately 12–31 amino acids adjacent to the transmembrane domain[1][2], forming two β-turns and a β-hairpin motif with unique glycosylation patterns. Overexpression and abnormal cleavage of MUC16, especially in malignancies, enhance cancer cell proliferation, apoptosis resistance, immune evasion, and metastasis[1][3][4]. Following proteolytic cleavage, the membrane-bound (retained) proximal ectodomain and C-terminal domain (MUC16-Cter) remain anchored, and can translocate to the nucleus where it is implicated in gene regulation[2]. Therapeutics targeting the MUC16 ectodomain (such as monoclonal antibodies and CAR-T therapies) are under development and may offer improved specificity and reduced off-target effects compared to those targeting the shed CA125 region[1][3]. The ectodomain is conserved across species and is being investigated as a selective therapeutic target for multiple cancers, especially high grade serous ovarian cancer[1][3].

Other names

MUC16CA125 antigen (the CA125 epitope is in the tandem repeat region, but "MUC16 ectodomain" is sometimes referenced as "MUC16 juxtamembrane domain," "membrane-proximal ectodomain of MUC16," "proximal MUC16 ectodomain," "MUC16-Cter")

Antibody-mediated immune response (antibody binding leads to cancer cell targeting and elimination); Immunotoxin delivery (antibody drug conjugates can deliver cytotoxic agents); Chimeric antigen receptor cell therapy (CAR-T cells engineered to target MUC16 ectodomain can lyse cancer cells); Inhibition of cell-surface MUC16 functions (blocking MUC16-mediated immune evasion and adhesion)