Mucin-1 (MUC1) (MUC1)

Mucin-1 (MUC1) is a high-molecular-weight type I transmembrane glycoprotein that is normally expressed on the apical surface of ductal epithelial cells, where it serves as a protective physical barrier and a lubricant [UniProt: P15941]. In healthy tissues, MUC1 is heavily O-glycosylated, which masks much of its protein core; however, in many cancers—particularly adenocarcinomas—MUC1 is overexpressed, loses its polarized distribution, and exhibits aberrant under-glycosylation [PMID: 28249130]. These changes expose tumor-specific peptide epitopes, such as the tandem repeat domain, and allow the MUC1 C-terminal subunit (MUC1-C) to interact with various intracellular signaling molecules like beta-catenin and NF-kappaB [PMID: 23412297]. These interactions promote oncogenic processes including cell survival, epithelial-to-mesenchymal transition (EMT), and resistance to chemotherapy. Consequently, MUC1 is a major therapeutic target, with drug development focusing on monoclonal antibodies, vaccines, and CAR-T cells that specifically recognize the tumor-associated glycoforms or inhibit the signaling activity of the MUC1-C subunit [PMID: 22961201].

Other names

CD227Epithelial membrane antigen (EMA)Polymorphic epithelial mucin (PEM)Cancer antigen 15-3 (CA 15-3)Krebs von den Lungen-6 (KL-6)H23AGPUMMUC-1Breast carcinoma-associated antigen DF3

Therapeutic strategies include monoclonal antibodies that bind the extracellular domain to induce antibody-dependent cellular cytotoxicity (ADCC), small molecule inhibitors that disrupt MUC1-C dimerization to block oncogenic signaling, and vaccines or CAR-T cells designed to trigger a T-cell mediated immune response against tumor-specific MUC1 epitopes [PMID: 30103151, PMID: 21947205].