MAGI1, short for membrane-associated guanylate kinase with inverted domain structure-1, is a cytoplasmic scaffolding protein. It stabilizes cell-to-cell contacts, regulating cadherin-mediated cell-cell adhesion in epithelial and endothelial cells. It is involved in crucial pathways like PI3K/AKT and Wnt/β-catenin, and is of great importance in tumor suppression and vascular functions. Genetic models, such as KO mouse models, can be valuable in studying its functions [1].

In various cancers, MAGI1 shows tumor-suppressive properties. In glioma, its low expression is related to malignant progression, and overexpression inhibits cell proliferation, migration, and invasion through regulating pathways like Akt, MMP2, MMP9, and E-cadherin/N-cadherin/vimentin [3]. In ER + breast cancer, MAGI1 loss leads to deeper quiescence/senescence, reduced DNA repair protein expression, and increased sensitivity to PARP1 inhibition. Also, in luminal breast cancer, MAGI1 acts as a tumor-suppressor by inhibiting the AMOTL2/p38 stress pathway [5,6]. In influenza A virus (IAV) infection, MAGI1 promotes infection by inhibiting interferon signaling. Depletion of MAGI1 suppresses IAV infection, indicating its potential as a therapeutic target for IAV-induced cardiovascular disease [2]. In endothelial cells, MAGI1 localizes at mature focal adhesion, regulating integrin-mediated adhesion and signaling. It also plays a role in endothelial cell activation and atherogenesis, with its phosphorylation and deSUMOylation regulating EC activation and apoptosis [4,7].

In conclusion, MAGI1 is a key protein with tumor-suppressive functions in multiple cancers and a role in viral infection and vascular-related diseases. Studies using gene-knockout models have revealed its importance in regulating cell proliferation, apoptosis, adhesion, and signaling pathways in these disease contexts, providing insights into potential therapeutic strategies.