MAGI1 inhibits the AMOTL2/p38 stress pathway and prevents luminal breast tumorigenesis

Kantar, Diala; Mur, Emilie Bousquet; Mancini, Maicol; Slaninova, Vera; Salah, Yezza Ben; Costa, Luca; Forest, Elodie; Lassus, Patrice; Géminard, Charles; Boissière‐Michot, Florence; Orsetti, Béatrice; Theillet, Charles; Colinge, Jacques; Bénistant, Christine; Maraver, Antonio; Héron-Milhavet, Lisa; Djiane, Alexandre

doi:10.1038/s41598-021-85056-1

Cited by 10 publications

(8 citation statements)

References 76 publications

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“…However, YAP also has some functions independent from transcription and we observed a stronger effect of YAP downregulation on adhesion sizes that on its classical target genes mRNA regulation. Maybe YAP localization in the nucleus is also to deplete it from the cytoplasm and to regulate its cytoplasmic functions as we recently described for the junctional protein MAG1 [ 59 ]. Additionally, there exists up to eight different YAP1 isoforms due to splicing and some may have different functions [ 60 ].…”

Section: Discussionmentioning

confidence: 99%

Mechanical Control of Cell Migration by the Metastasis Suppressor Tetraspanin CD82/KAI1

Ordas

Costa

Lozano

et al. 2021

Cells

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The plasma membrane is a key actor of cell migration. For instance, its tension controls persistent cell migration and cell surface caveolae integrity. Then, caveolae constituents such as caveolin-1 can initiate a mechanotransduction loop that involves actin- and focal adhesion-dependent control of the mechanosensor YAP to finely tune cell migration. Tetraspanin CD82 (also named KAI-1) is an integral membrane protein and a metastasis suppressor. Its expression is lost in many cancers including breast cancer. It is a strong inhibitor of cell migration by a little-known mechanism. We demonstrated here that CD82 controls persistent 2D migration of EGF-induced single cells, stress fibers and focal adhesion sizes and dynamics. Mechanistically, we found that CD82 regulates membrane tension, cell surface caveolae abundance and YAP nuclear translocation in a caveolin-1-dependent manner. Altogether, our data show that CD82 controls 2D cell migration using membrane-driven mechanics involving caveolin and the YAP pathway.

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Section: Discussionmentioning

confidence: 99%

Mechanical Control of Cell Migration by the Metastasis Suppressor Tetraspanin CD82/KAI1

Ordas

Costa

Lozano

et al. 2021

Cells

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“…Primary antibodies used are listed below. Secondary Alexa Fluor Antibodies (1/600; Invitrogen) were used as described previously (Kantar et al, 2021) for 1 hour at room temperature before mounting the coverslips with Vectashield (Vector Laboratories #H-1200) and imaging on Zeiss Apotome or Leica Thunder microscopes.…”

Section: Immunofluorescencementioning

confidence: 99%

The Hippo pathway terminal effector TAZ/WWTR1 mediates oxaliplatin sensitivity in colon cancer cells

Slaninova

Héron-Milhavet

Robin

et al. 2023

Preprint

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YAP and TAZ, the Hippo pathway terminal transcriptional activators, are frequently upregulated in cancers. In tumor cells, they have been mainly associated with increased tumorigenesis controlling different aspects from cell cycle regulation, stemness, or resistance to chemotherapies. In fewer cases, they have also been shown to oppose cancer progression, including by promoting cell death through the action of the P73/YAP transcriptional complex, in particular after chemotherapeutic drug exposure. We show here that oxaliplatin treatment on colorectal cancer HCT116 cells led to a dramatic core Hippo pathway down-regulation and nuclear accumulation of TAZ. We further show that TAZ was required for the increased sensitivity of HCT116 cells to oxaliplatin, an effect that appeared independent of P73, but which required the nuclear relocalization of TAZ. Our results support thus an early action of TAZ to sensitize cells to oxaliplatin, consistent with a model in which nuclear TAZ in the context of DNA damage and P53 activity pushes cells towards apoptosis.

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“…A similar study that also evaluated the expression of MAGI1 in BC cell lines confirmed its tumor suppressive function and found a distinct molecular mechanism behind this effect. The study reported that loss of MAGI1 leads to cellular accumulation of E-cadherin and the actin binding scaffold AMOTL2, resulting in increased stiffness, which in turn downregulates yes-associated protein 1 (YAP) activity, the terminal Hippo-pathway effector, and increases rho-associated protein kinase (ROCK) and p38 stress activated protein kinase activities [62].…”

Section: Magi1 Role As Tumor Suppressormentioning

confidence: 99%

MAGI1, a Scaffold Protein with Tumor Suppressive and Vascular Functions

Wörthmüller

Rüegg

2021

Cells

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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.

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MAGI1 inhibits the AMOTL2/p38 stress pathway and prevents luminal breast tumorigenesis

Cited by 10 publications

References 76 publications

Mechanical Control of Cell Migration by the Metastasis Suppressor Tetraspanin CD82/KAI1

Mechanical Control of Cell Migration by the Metastasis Suppressor Tetraspanin CD82/KAI1

The Hippo pathway terminal effector TAZ/WWTR1 mediates oxaliplatin sensitivity in colon cancer cells

MAGI1, a Scaffold Protein with Tumor Suppressive and Vascular Functions

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