Mucin 1, C-terminal subunit (MUC1*) (MUC1*)

MUC1* is the truncated, transmembrane C-terminal subunit of Mucin 1 (MUC1) that remains on the cell surface after the N-terminal extracellular domain is enzymatically shed by metalloproteinases like ADAM17 (UniProt: P15941; PubMed: 19851537). Unlike the full-length MUC1 found on healthy epithelial cells, MUC1* functions as a potent oncogenic growth factor receptor that is primarily activated through dimerization (PubMed: 21479210). This cleavage event exposes a specific neoepitope, often referred to as the PSMGFR sequence, which is hidden in the full-length protein and thus absent from normal tissues, making it a highly selective target for malignancy (PubMed: 18843355). Activation of MUC1* by ligands such as NME7 triggers downstream signaling cascades, including the PI3K/Akt and Ras/MAPK pathways, which drive tumor cell proliferation, survival, and the maintenance of cancer stem cell pluripotency (PubMed: 18843355; Minerva Biotechnologies, 2024). Because the MUC1* neoepitope is specifically exposed on a wide variety of solid tumors but not on healthy cells, it has become a high-priority target for next-generation immunotherapies. Current therapeutic strategies include CAR-T cells, such as HuMUC1*-CAR-T, and monoclonal antibodies designed to recognize this specific neoepitope to induce tumor cell lysis while sparing normal epithelial tissues (ClinicalTrials.gov: NCT04020575). Research indicates that MUC1* is not only a marker of cancer but a functional driver of the epithelial-to-mesenchymal transition (EMT) and metastasis, further validating its role as a critical therapeutic target in oncology (PubMed: 21479210).

Other names

MUC1-CMucin 1 C-terminal subunitCleaved Mucin 1MUC1-starCD227EpisialinTumor-associated epithelial mucinPSMGFR

Targeting the neoepitope exposed upon cleavage of the MUC1 extracellular domain to induce cell death via CAR-T mediated lysis or antibody-dependent cellular cytotoxicity (ADCC), and inhibiting the dimerization-induced signaling of the MUC1* receptor (Minerva Biotechnologies, 2024; PubMed: 21479210).