MAGI1 localizes to mature focal adhesion and modulates endothelial cell adhesion, migration and angiogenesis

Alday-Parejo, Begoña; Ghimire, Kedar; Coquoz, Oriana; Albisetti, Gioele W.; Tamò, Luca; Zarić, Jelena; Stalin, Jimmy; Rüegg, Curzio

doi:10.1080/19336918.2021.1911472

Cited by 13 publications

(13 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recently, MAGI1 was found present in mature focal adhesions in HUVEC cells in colo-calization with the known focal adhesion-associated molecules paxillin, α-actinin and β3-integrin. Experimental downregulation of MAGI1 in HUVEC reduced focal adhesion formation and maturation, cell spreading, actin stress fiber formation, and RhoA/Rac activation [76]. This is consistent with MAGI1 contributing to regulate focal adhesion maturation.…”

Section: Magi1 Vascular Functionssupporting

confidence: 76%

“…Likewise, MAGI1 was shown to bind to PRKX, a protein kinase that modulates angiogenesis, however, if MAGI1 regulates PRKX functions through this interaction needs further evaluation [75]. A recent study showed that MAGI1 downregulation in ECs promotes pseudocapillary and endothelial network formation, while MAGI1 overexpression reduces endothelial cell tubulogenesis in vitro and angiogenesis in vivo in a transgenic mouse model [76].…”

Section: Magi1 Vascular Functionsmentioning

confidence: 99%

“…MAGI1 colocalizes to mature focal adhesions in ECs and regulates integrin-dependent cell adhesion and migration [76]. Many questions arise concerning this point, like how MAGI1 is recruited to focal adhesions; how it regulates focal adhesion maturation; and which are the binding partners that interact with MAGI1 in the adhesiome.…”

Section: Regulation Of Endothelial Functionmentioning

confidence: 99%

See 2 more Smart Citations

MAGI1, a Scaffold Protein with Tumor Suppressive and Vascular Functions

Wörthmüller

Rüegg

2021

Cells

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Magi1 Vascular Functionssupporting

confidence: 76%

Section: Magi1 Vascular Functionsmentioning

confidence: 99%

Section: Regulation Of Endothelial Functionmentioning

confidence: 99%

See 1 more Smart Citation

MAGI1, a Scaffold Protein with Tumor Suppressive and Vascular Functions

Wörthmüller

Rüegg

2021

Cells

Self Cite

View full text Add to dashboard Cite

show abstract

“…Adjacent to the plasma membrane, paxillin, focal adhesion kinase (FAK), cellular sarcoma (c-Src, herein Src), kindlin 1 and the talin head domain (N-terminus) co-localise with integrin cytoplasmic tails inside the integrin signalling layer. Talin (C-terminus) and vinculin build the intermediate force transduction layer, whereas actin binding proteins (>50 nm beneath the plasma membrane), including vinculin, zyxin, α-actinin and vasodilatator-stimulated phosphoprotein, in conjunction with actin, form the actin regulatory layer ( Refs 101,[148][149][150][151][152].…”

Section: Integrins and Their Role In Cartilage Mechanotransductionmentioning

confidence: 99%

Integrins, cadherins and channels in cartilage mechanotransduction: perspectives for future regeneration strategies

Dieterle

Husari

Rolauffs

et al. 2021

Expert Rev. Mol. Med.

View full text Add to dashboard Cite

Articular cartilage consists of hyaline cartilage, is a major constituent of the human musculoskeletal system and has critical functions in frictionless joint movement and articular homoeostasis. Osteoarthritis (OA) is an inflammatory disease of articular cartilage, which promotes joint degeneration. Although it affects millions of people, there are no satisfying therapies that address this disease at the molecular level. Therefore, tissue regeneration approaches aim at modifying chondrocyte biology to mitigate the consequences of OA. This requires appropriate biochemical and biophysical stimulation of cells. Regarding the latter, mechanotransduction of chondrocytes and their precursor cells has become increasingly important over the last few decades. Mechanotransduction is the transformation of external biophysical stimuli into intracellular biochemical signals, involving sensor molecules at the cell surface and intracellular signalling molecules, so-called mechano-sensors and -transducers. These signalling events determine cell behaviour. Mechanotransducing ion channels and gap junctions additionally govern chondrocyte physiology. It is of great scientific and medical interest to induce a specific cell behaviour by controlling these mechanotransduction pathways and to translate this knowledge into regenerative clinical therapies. This review therefore focuses on the mechanotransduction properties of integrins, cadherins and ion channels in cartilaginous tissues to provide perspectives for cartilage regeneration.

show abstract

“…In endothelial cells, MAGI1 promotes focal adhesion maturation and reduces its turnover. This process involves increased endothelial cells adhesion to the extracellular matrix, via the transient increase in both RhoA and Rac1 activities, and reduces invasiveness and tubulogenesis in vitro, and suppresses angiogenesis in vivo [ 196 ].…”

Section: Implication Of Magi Molecular Scaffolds In the Control Of Carcinogenesismentioning

confidence: 99%

A New Story of the Three Magi: Scaffolding Proteins and lncRNA Suppressors of Cancer

Kotelevets

Chastre

2021

Cancers

View full text Add to dashboard Cite

Scaffolding molecules exert a critical role in orchestrating cellular response through the spatiotemporal assembly of effector proteins as signalosomes. By increasing the efficiency and selectivity of intracellular signaling, these molecules can exert (anti/pro)oncogenic activities. As an archetype of scaffolding proteins with tumor suppressor property, the present review focuses on MAGI1, 2, and 3 (membrane-associated guanylate kinase inverted), a subgroup of the MAGUK protein family, that mediate networks involving receptors, junctional complexes, signaling molecules, and the cytoskeleton. MAGI1, 2, and 3 are comprised of 6 PDZ domains, 2 WW domains, and 1 GUK domain. These 9 protein binding modules allow selective interactions with a wide range of effectors, including the PTEN tumor suppressor, the β-catenin and YAP1 proto-oncogenes, and the regulation of the PI3K/AKT, the Wnt, and the Hippo signaling pathways. The frequent downmodulation of MAGIs in various human malignancies makes these scaffolding molecules and their ligands putative therapeutic targets. Interestingly, MAGI1 and MAGI2 genetic loci generate a series of long non-coding RNAs that act as a tumor promoter or suppressor in a tissue-dependent manner, by selectively sponging some miRNAs or by regulating epigenetic processes. Here, we discuss the different paths followed by the three MAGIs to control carcinogenesis.

show abstract

MAGI1 localizes to mature focal adhesion and modulates endothelial cell adhesion, migration and angiogenesis

Cited by 13 publications

References 53 publications

MAGI1, a Scaffold Protein with Tumor Suppressive and Vascular Functions

MAGI1, a Scaffold Protein with Tumor Suppressive and Vascular Functions

Integrins, cadherins and channels in cartilage mechanotransduction: perspectives for future regeneration strategies

A New Story of the Three Magi: Scaffolding Proteins and lncRNA Suppressors of Cancer

Contact Info

Product

Resources

About