Mucin 1, cell surface associated (MUC1) (MUC1)

Mucin 1 (MUC1) is a heterodimeric transmembrane glycoprotein that is normally expressed on the apical surface of epithelial cells, where it provides a protective barrier and participates in cell signaling. In pancreatic ductal adenocarcinoma (PDAC), MUC1 is characteristically overexpressed, loses its polarized distribution, and undergoes aberrant glycosylation, making it a prominent tumor-associated antigen. The protein is cleaved into two subunits: the large N-terminal extracellular subunit (MUC1-N) and the smaller C-terminal transmembrane subunit (MUC1-C). The MUC1-C extracellular domain is particularly significant in PDAC as it facilitates the formation of complexes with receptor tyrosine kinases (like EGFR and HER2) and mediates oncogenic signaling that promotes tumor cell survival, invasion, and resistance to chemotherapy. Targeting the MUC1-C subunit is a major focus in oncology because it remains anchored to the cell membrane, unlike the shed MUC1-N subunit, and directly contributes to the metabolic and epigenetic reprogramming of cancer cells. Therapeutic approaches include monoclonal antibodies, small molecule inhibitors like GO-203 that block MUC1-C oligomerization, and advanced cellular therapies such as CAR-T cells designed to recognize tumor-specific MUC1 glycoforms.

Other names

CD227Epithelial membrane antigen (EMA)Polymorphic epithelial mucin (PEM)MUC1-CMUC1-NTumor-associated epithelial mucinH23AGPUMKL-6MAM6

Inhibition of MUC1-C oligomerization, antibody-dependent cellular cytotoxicity (ADCC), CAR-T cell-mediated lysis, blockade of oncogenic signaling pathways (Wnt/beta-catenin, NF-kappaB, and PI3K/Akt), and disruption of redox homeostasis.