MAGI1, a Scaffold Protein with Tumor Suppressive and Vascular Functions
MAGI1 is a cytoplasmic scaffolding protein initially identified as a component of cell-to-cell contacts stabilizing cadherin-mediated cell–cell adhesion in epithelial and endothelial cells. Clinical-pathological and experimental evidence indicates that MAGI1 expression is decreased in some inflammat...
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doaj-a6d7d3be195c49c59b42e9f2de6490102021-07-01T00:08:44ZengMDPI AGCells2073-44092021-06-01101494149410.3390/cells10061494MAGI1, a Scaffold Protein with Tumor Suppressive and Vascular FunctionsJanine Wörthmüller0Curzio Rüegg1Laboratory of Experimental and Translational Oncology, Pathology, Department of Oncology, Microbiology and Immunology (OMI), Faculty of Science and Medicine, University of Fribourg, CH-1700 Fribourg, SwitzerlandLaboratory of Experimental and Translational Oncology, Pathology, Department of Oncology, Microbiology and Immunology (OMI), Faculty of Science and Medicine, University of Fribourg, CH-1700 Fribourg, SwitzerlandMAGI1 is a cytoplasmic scaffolding protein initially identified as a component of cell-to-cell contacts stabilizing cadherin-mediated cell–cell adhesion in epithelial and endothelial cells. Clinical-pathological and experimental evidence indicates that MAGI1 expression is decreased in some inflammatory diseases, and also in several cancers, including hepatocellular carcinoma, colorectal, cervical, breast, brain, and gastric cancers and appears to act as a tumor suppressor, modulating the activity of oncogenic pathways such as the PI3K/AKT and the Wnt/β-catenin pathways. Genomic mutations and other mechanisms such as mechanical stress or inflammation have been described to regulate MAGI1 expression. Intriguingly, in breast and colorectal cancers, MAGI1 expression is induced by non-steroidal anti-inflammatory drugs (NSAIDs), suggesting a role in mediating the tumor suppressive activity of NSAIDs. More recently, MAGI1 was found to localize at mature focal adhesion and to regulate integrin-mediated adhesion and signaling in endothelial cells. Here, we review MAGI1′s role as scaffolding protein, recent developments in the understanding of MAGI1 function as tumor suppressor gene, its role in endothelial cells and its implication in cancer and vascular biology. We also discuss outstanding questions about its regulation and potential translational implications in oncology.https://www.mdpi.com/2073-4409/10/6/1494breast cancertumor suppressorPTENPI3K/AKTWntfocal adhesions |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Janine Wörthmüller Curzio Rüegg |
spellingShingle |
Janine Wörthmüller Curzio Rüegg MAGI1, a Scaffold Protein with Tumor Suppressive and Vascular Functions Cells breast cancer tumor suppressor PTEN PI3K/AKT Wnt focal adhesions |
author_facet |
Janine Wörthmüller Curzio Rüegg |
author_sort |
Janine Wörthmüller |
title |
MAGI1, a Scaffold Protein with Tumor Suppressive and Vascular Functions |
title_short |
MAGI1, a Scaffold Protein with Tumor Suppressive and Vascular Functions |
title_full |
MAGI1, a Scaffold Protein with Tumor Suppressive and Vascular Functions |
title_fullStr |
MAGI1, a Scaffold Protein with Tumor Suppressive and Vascular Functions |
title_full_unstemmed |
MAGI1, a Scaffold Protein with Tumor Suppressive and Vascular Functions |
title_sort |
magi1, a scaffold protein with tumor suppressive and vascular functions |
publisher |
MDPI AG |
series |
Cells |
issn |
2073-4409 |
publishDate |
2021-06-01 |
description |
MAGI1 is a cytoplasmic scaffolding protein initially identified as a component of cell-to-cell contacts stabilizing cadherin-mediated cell–cell adhesion in epithelial and endothelial cells. Clinical-pathological and experimental evidence indicates that MAGI1 expression is decreased in some inflammatory diseases, and also in several cancers, including hepatocellular carcinoma, colorectal, cervical, breast, brain, and gastric cancers and appears to act as a tumor suppressor, modulating the activity of oncogenic pathways such as the PI3K/AKT and the Wnt/β-catenin pathways. Genomic mutations and other mechanisms such as mechanical stress or inflammation have been described to regulate MAGI1 expression. Intriguingly, in breast and colorectal cancers, MAGI1 expression is induced by non-steroidal anti-inflammatory drugs (NSAIDs), suggesting a role in mediating the tumor suppressive activity of NSAIDs. More recently, MAGI1 was found to localize at mature focal adhesion and to regulate integrin-mediated adhesion and signaling in endothelial cells. Here, we review MAGI1′s role as scaffolding protein, recent developments in the understanding of MAGI1 function as tumor suppressor gene, its role in endothelial cells and its implication in cancer and vascular biology. We also discuss outstanding questions about its regulation and potential translational implications in oncology. |
topic |
breast cancer tumor suppressor PTEN PI3K/AKT Wnt focal adhesions |
url |
https://www.mdpi.com/2073-4409/10/6/1494 |
work_keys_str_mv |
AT janineworthmuller magi1ascaffoldproteinwithtumorsuppressiveandvascularfunctions AT curzioruegg magi1ascaffoldproteinwithtumorsuppressiveandvascularfunctions |
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