Mucin 1, cell surface associated, C-terminal subunit (MUC1-C)

Mucin 1, cell surface associated, C-terminal subunit (MUC1-C) is a transmembrane oncoprotein derived from the proteolytic cleavage of the MUC1 heterodimer. Unlike the heavily glycosylated N-terminal subunit (MUC1-N) that provides a physical barrier on epithelial surfaces, MUC1-C functions as a dynamic signaling component that localizes to the plasma membrane, mitochondria, and nucleus [1][2]. In healthy cells, MUC1-C is restricted to the apical membrane of polarized epithelium, but in cancer, it is overexpressed and loses polarity, allowing it to interact with and activate various pro-survival pathways including Wnt/beta-catenin, NF-kappaB, and STAT3 [2][3]. These interactions promote the epithelial-mesenchymal transition (EMT), cancer stem cell self-renewal, and resistance to apoptosis and DNA-damaging agents [3][4]. Consequently, MUC1-C is a high-priority therapeutic target in multiple malignancies, including breast, lung, and pancreatic cancers [1][5]. Current pharmacological strategies include small peptide inhibitors like GO-203 that block MUC1-C dimerization, monoclonal antibodies, and chimeric antigen receptor (CAR) T-cell therapies designed to exploit its tumor-specific surface exposure [4][6]. Sources: [1] UniProt Consortium. "UniProtKB - P15941 (MUC1_HUMAN)." [2] Kufe, D. W. "MUC1-C oncoprotein as a target in cancer." British Journal of Cancer (2013). [3] Raina, D., et al. "The MUC1-C oncoprotein is a target for the treatment of breast cancer." Cancer Research (2009). [4] Alam, M., et al. "MUC1-C effector function in cancer stem cells." Molecular Cancer Research (2014). [5] ClinicalTrials.gov. "A Study of GO-203 in Patients With Advanced Solid Tumors." [6] Zhou, R., et al. "MUC1-C-targeted CAR T cells for the treatment of solid tumors." Journal of Hematology & Oncology (2019).

Other names

MUC1-CMUC1 C-terminal subunitCD227Epithelial membrane antigenPolymorphic epithelial mucinPEMEMAH23AGPUMBreast carcinoma-associated antigen DF3

Inhibition of MUC1-C oligomerization and nuclear translocation, blocking of oncogenic signaling pathways (NF-kappaB, STAT, Wnt/beta-catenin), and induction of antibody-dependent cellular cytotoxicity (ADCC) or T-cell mediated lysis.