The network map of mucin 1 mediated signaling in cancer progression and immune modulation.

Abstract

Mucin 1 (MUC1) is a type-I transmembrane glycoprotein, ranked as the second most promising cancer antigen for therapeutic development by the National Cancer Institute. Recently, MUC1 has gained significant attention as a therapeutic target in cancer immunotherapy. Thus, understanding MUC1-regulated signaling is essential for advancing therapeutic strategies. Since existing pathway repositories lack a comprehensive MUC1 signaling map, we constructed one by manually annotating experimentally validated signaling events from 115 articles following NetPath annotation criteria. Considering the topology of annotated molecules, a pathway map was developed using the PathVisio software. This pathway map is a valuable resource cataloguing 209 molecules and 690 signaling events, of which 395 events are unique. The catalogued reactions include 118 enzyme catalysis events, 133 molecular associations, 132 gene regulation events, 216 protein expressions, 49 activation/inhibition and 42 protein translocation events. MUC1 signaling pathway showed significant cross-talk with Wnt/β-catenin, NF-κB, PI3K-AKT, and MAPK signaling. The aberrant expression of MUC1 is associated with proliferation, metastasis, angiogenesis and invasion in various cancers, such as breast, lung, pancreatic, colon, oral, prostate, ovarian, and gastric cancers. Moreover, it also regulates the proliferation and function of immune cells, including myeloid-derived suppressor cells, tumour-associated macrophages, dendritic cells, CD4 + T-cells and CD8 + T-cells. This pathway map may serve as a valuable reference for understanding MUC1-driven oncogenic and immunomodulatory mechanisms, providing insights for developing novel therapeutic strategies for cancer treatment.