TRIP6, a novel molecular partner of the MAGI‐1 scaffolding molecule, promotes invasiveness

Chastre, Eric; Mahmoud, Abdessamad; Kruglov, Alexey G.; Bruyneel, Erik; Bracke, Marc; Gioia, Yolande Di; Beckerle, Mary C.; Roy, Frans van; Kotelevets, Larissa

doi:10.1096/fj.08-106344

Cited by 60 publications

(67 citation statements)

References 35 publications

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“…These results suggest that MAGI1 modulates morphological and functional (that is, invasion and migration) features independently of epithelial-to-mesenchymal transition. E-cadherin/b-catenin complexes are forming a signalosome that recruits multiple scaffolding molecules such as MAGI1, PTEN (Kotelevets et al, 2005), Rap1 (Mino et al, 2000) and TRIP6 (Chastre et al, 2009). The stabilization of E-cadherin/b-catenin at the cell-cell borders by MAGI1 overexpression and its loss from cell-cell borders following MAGI1 silencing is consistent with the model that MAGI1 suppresses Wnt/b-catenin signaling by decreasing the pool of free b-catenin.…”

Section: Magi1 As a Coxib-induced Tumor-suppressor Protein In Crc Celsupporting

confidence: 81%

“…MAGI1 suppresses the invasiveness of Madin-Darby Canine Kidney (MDCK) cells by recruiting PTEN to cell-cell contacts and decreasing phosphatidylinositol-3-OH kinase signaling (Kotelevets et al, 2005). TRIP6 has been identified as a binding partner of MAGI1b in epithelial cells that promotes MDCK invasiveness through the activation of nuclear factor-kB and Akt (Chastre et al, 2009). Taken together, MAGI1 is an important molecule for the stabilization of cadherinmediated cell-cell interactions and the suppression of invasiveness in non-transformed epithelial cells.…”

Section: Introductionmentioning

confidence: 99%

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Identification of MAGI1 as a tumor-suppressor protein induced by cyclooxygenase-2 inhibitors in colorectal cancer cells

et al. 2011

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Cyclooxyganase-2 (COX-2), a rate-limiting enzyme in the prostaglandin synthesis pathway, is overexpressed in many cancers and contributes to cancer progression through tumor cell-autonomous and paracrine effects. Regular use of non-steroidal anti-inflammatory drugs or selective COX-2 inhibitors (COXIBs) reduces the risk of cancer development and progression, in particular of the colon. The COXIB celecoxib is approved for adjunct therapy in patients with Familial adenomatous polyposis at high risk for colorectal cancer (CRC) formation. Long-term use of COXIBs, however, is associated with potentially severe cardiovascular complications, which hampers their broader use as preventive anticancer agents. In an effort to better understand the tumor-suppressive mechanisms of COXIBs, we identified MAGUK with Inverted domain structure-1 (MAGI1), a scaffolding protein implicated in the stabilization of adherens junctions, as a gene upregulated by COXIB in CRC cells and acting as tumor suppressor. Overexpression of MAGI1 in CRC cell lines SW480 and HCT116 induced an epitheliallike morphology; stabilized E-cadherin and b-catenin localization at cell-cell junctions; enhanced actin stress fiber and focal adhesion formation; increased cell adhesion to matrix proteins and suppressed Wnt signaling, anchorage-independent growth, migration and invasion in vitro. Conversely, MAGI1 silencing decreased Ecadherin and b-catenin localization at cell-cell junctions; disrupted actin stress fiber and focal adhesion formation; and enhanced Wnt signaling, anchorage-independent growth, migration and invasion in vitro. MAGI1 overexpression suppressed SW480 and HCT116 subcutaneous primary tumor growth, attenuated primary tumor growth and spontaneous lung metastasis in an orthotopic model of CRC, and decreased the number and size of metastatic nodules in an experimental model of lung metastasis. Collectively, these results identify MAG1 as a COXIBinduced inhibitor of the Wnt/b-catenin signaling pathway, with tumor-suppressive and anti-metastatic activity in experimental colon cancer.

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Section: Magi1 As a Coxib-induced Tumor-suppressor Protein In Crc Celsupporting

confidence: 81%

Section: Introductionmentioning

confidence: 99%

Identification of MAGI1 as a tumor-suppressor protein induced by cyclooxygenase-2 inhibitors in colorectal cancer cells

et al. 2011

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“…However, unlike STOML2 and FECH, TRIP6 is connected to b-catenin in the literature, the main signaling pathway in desmoid tumors. Indeed, TRIP6 might compete with b-catenin for binding with the MAGI-1b/PTEN signalosome to destabilize E-cadherin junctional complexes and to promote cell motility through the regulation of Akt/NF-kB targets and/or effectors of focal adhesion (33). STOML2 and FECH are likely b-catenin transcriptional targets.…”

Section: Discussionmentioning

confidence: 99%

Gene Expression Profiling of Desmoid Tumors by cDNA Microarrays and Correlation with Progression-Free Survival

Salas

Brulard

Terrier

et al. 2015

Clinical Cancer Research

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Purpose: Because desmoid tumors exhibit an unpredictable clinical course, translational research is crucial to identify the predictive factors of progression in addition to the clinical parameters. The main issue is to detect patients who are at a higher risk of progression. The aim of this work was to identify molecular markers that can predict progression-free survival (PFS).Experimental Design: Gene-expression screening was conducted on 115 available independent untreated primary desmoid tumors using cDNA microarray. We established a prognostic gene-expression signature composed of 36 genes. To test robustness, we randomly generated 1,000 36-gene signatures and compared their outcome association to our define 36-genes molecular signature and we calculated positive predictive value (PPV) and negative predictive value (NPV).Results: Multivariate analysis showed that our molecular signature had a significant impact on PFS while no clinical factor had any prognostic value. Among the 1,000 random signatures generated, 56.7% were significant and none was more significant than our 36-gene molecular signature. PPV and NPV were high (75.58% and 81.82%, respectively). Finally, the top two genes downregulated in no-recurrence were FECH and STOML2 and the top gene upregulated in no-recurrence was TRIP6.Conclusions: By analyzing expression profiles, we have identified a gene-expression signature that is able to predict PFS. This tool may be useful for prospective clinical studies.

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“…The perimeters of these actin rings were unchanged (data not shown). Because knockdown of TRIP6 has been associated with changes in activity of Rho family GTPases (33,34) and RhoA plays a critical role in osteoclast sealing zone formation (35,36), we tested whether knockdown of TRIP6 in osteoclasts resulted in altered RhoA activity. Fig.…”

Section: Trip6 Suppression Alters Sealing Zone Dimensions and Decreasesmentioning

confidence: 99%

c-Src-mediated Phosphorylation of Thyroid Hormone Receptor-interacting Protein 6 (TRIP6) Promotes Osteoclast Sealing Zone Formation

McMichael

Meyer

Lee

2010

Journal of Biological Chemistry

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Osteoclasts resorb bone through the formation of a unique attachment structure called the sealing zone. In this study, a role for thyroid hormone receptor-interacting protein 6 (TRIP6) in sealing zone formation and osteoclast activity was examined. TRIP6 was shown to reside in the sealing zone through its association with tropomyosin 4, an actin-binding protein that regulates sealing dimensions and bone resorptive capacity. Suppression of TRIP6 in mature osteoclasts by RNA interference altered sealing zone dimensions and inhibited bone resorption, whereas overexpression of TRIP6 increased the sealing zone perimeter and enhanced bone resorption. Treatment of osteoclasts with lysophosphatidic acid (LPA), which phosphorylates TRIP6 at tyrosine 55 through a c-Src-dependent mechanism, caused increased association of TRIP6 with the sealing zone, as did overexpression of a TRIP6 cDNA bearing a phosphomimetic mutation at tyrosine 55. Further, LPA treatment caused increases in osteoclast fusion, sealing zone perimeter, and bone resorptive capacity. In contrast, overexpression of TRIP6 containing a nonphosphorylatable amino acid residue at position 55 severely diminished sealing zone formation and bone resorption and suppressed the effects of LPA on the cytoskeleton. LPA effects were mediated through its receptor isoform LPA(2), as indicated by treatments with receptor-specific agonists and antagonists. Thus, these studies suggest that TRIP6 is a critical downstream regulator of c-Src signaling and that its phosphorylation is permissive for its presence in the sealing zone where it plays a positive role in osteoclast bone resorptive capacity.

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TRIP6, a novel molecular partner of the MAGI‐1 scaffolding molecule, promotes invasiveness

Cited by 60 publications

References 35 publications

Identification of MAGI1 as a tumor-suppressor protein induced by cyclooxygenase-2 inhibitors in colorectal cancer cells

Identification of MAGI1 as a tumor-suppressor protein induced by cyclooxygenase-2 inhibitors in colorectal cancer cells

Gene Expression Profiling of Desmoid Tumors by cDNA Microarrays and Correlation with Progression-Free Survival

c-Src-mediated Phosphorylation of Thyroid Hormone Receptor-interacting Protein 6 (TRIP6) Promotes Osteoclast Sealing Zone Formation

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