Magi1-KO Mouse

Magi1, short for membrane-associated guanylate kinase with inverted domain structure-1, is a cytoplasmic scaffolding protein. It is crucial for stabilizing cell-to-cell contacts, especially cadherin-mediated adhesion in epithelial and endothelial cells. It is involved in multiple oncogenic pathways such as the PI3K/AKT and the Wnt/β-catenin pathways, and is considered a potential tumor suppressor gene [1,3,4,6,7,8].

In Magi1-depleted endothelial cells, there is an increase in protein expression and signaling networks related to interferon production, and Magi1 depletion suppresses influenza A virus (IAV) infection, indicating Magi1 promotes IAV infection by inhibiting anti-viral responses [2]. In ER+ breast cancer cell lines, deletion of Magi1 leads to cells entering a deeper level of quiescence/senescence, reduced DNA repair protein expression, and increased sensitivity to PARP1 inhibition. In human ER+ breast cancer patients, low Magi1 levels are associated with a higher tumor mutational burden and homologous recombination deficiency [3]. In glioma cells, overexpression of Magi1 inhibits cell proliferation, migration, and invasion by regulating related pathways [4]. In Magi1 -/+ mice, reduced Magi1 expression inhibits disturbed flow-induced atherogenesis, suggesting Magi1 is involved in the development of atherosclerosis [5].

In conclusion, Magi1 has essential functions in maintaining cell-cell adhesion and is involved in multiple disease-related processes. Through gene knockout or knockdown models in cells and mice, its roles in promoting IAV infection, preventing senescence and promoting DNA damage response in ER+ breast cancer, inhibiting glioma cell progression, and driving atherosclerosis have been revealed. These findings contribute to understanding the pathogenesis of related diseases and may provide new therapeutic targets.

References:

1. Wörthmüller, Janine, Rüegg, Curzio. 2021. MAGI1, a Scaffold Protein with Tumor Suppressive and Vascular Functions. In Cells, 10, . doi:10.3390/cells10061494. https://pubmed.ncbi.nlm.nih.gov/34198584/

2. Wang, Yin, Abe, Jun-Ichi, Chau, Khanh M, Evans, Scott E, Le, Nhat-Tu. 2022. MAGI1 inhibits interferon signaling to promote influenza A infection. In Frontiers in cardiovascular medicine, 9, 791143. doi:10.3389/fcvm.2022.791143. https://pubmed.ncbi.nlm.nih.gov/36082118/

3. Wörthmüller, Janine, Disler, Simona, Pradervand, Sylvain, Desmedt, Christine, Rüegg, Curzio. 2023. MAGI1 Prevents Senescence and Promotes the DNA Damage Response in ER+ Breast Cancer. In Cells, 12, . doi:10.3390/cells12151929. https://pubmed.ncbi.nlm.nih.gov/37566008/

4. Li, Zhong-Yan, Li, Xue-Hua, Tian, Guang-Wei, Gao, Hai, Wang, Zhen-Yu. 2019. MAGI1 Inhibits the Proliferation, Migration and Invasion of Glioma Cells. In OncoTargets and therapy, 12, 11281-11290. doi:10.2147/OTT.S230236. https://pubmed.ncbi.nlm.nih.gov/31908493/

5. Abe, Jun-Ichi, Ko, Kyung Ae, Kotla, Sivareddy, Evans, Scott E, Le, Nhat-Tu. 2019. MAGI1 as a link between endothelial activation and ER stress drives atherosclerosis. In JCI insight, 4, . doi:10.1172/jci.insight.125570. https://pubmed.ncbi.nlm.nih.gov/30944250/

6. Kantar, Diala, Mur, Emilie Bousquet, Mancini, Maicol, Heron-Milhavet, Lisa, Djiane, Alexandre. 2021. MAGI1 inhibits the AMOTL2/p38 stress pathway and prevents luminal breast tumorigenesis. In Scientific reports, 11, 5752. doi:10.1038/s41598-021-85056-1. https://pubmed.ncbi.nlm.nih.gov/33707576/

7. Alday-Parejo, Begoña, Richard, François, Wörthmüller, Janine, Santamaria-Martinez, Albert, Rüegg, Curzio. 2020. MAGI1, a New Potential Tumor Suppressor Gene in Estrogen Receptor Positive Breast Cancer. In Cancers, 12, . doi:10.3390/cancers12010223. https://pubmed.ncbi.nlm.nih.gov/31963297/

8. Feng, Xuemin, Jia, Shuqin, Martin, Tracey A, Jiang, Wen G. . Regulation and involvement in cancer and pathological conditions of MAGI1, a tight junction protein. In Anticancer research, 34, 3251-6. doi:. https://pubmed.ncbi.nlm.nih.gov/24982328/