Transforming Growth Factor β Induces Rosettes of Podosomes in Primary Aortic Endothelial Cells

Varon, Christine; Tatin, Florence; Moreau, Violaine; Obberghen-Schilling, Ellen Van; Fernandez-Sauze, Samantha; Reuzeau, Edith; Kramer, IJsbrand M.; Génot, Elisabeth

doi:10.1128/mcb.26.9.3582-3594.2006

Cited by 153 publications

(176 citation statements)

References 62 publications

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“…Many podosomal components, such as cortactin, focal adhesion kinase or vinculin are Src substrates. Consequently, pharmacological agents targeting Src activity affect podosome formation (Linder et al, 2000;Tatin et al, 2006;Varon et al, 2006). Indeed, consistent with previous reports, NaF-induced podosomes were found to be sensitive to PP1.…”

Section: Discussionsupporting

confidence: 78%

Sodium fluoride induces podosome formation in endothelial cells

Tatin

Grise

Reuzeau

et al. 2010

Biology of the Cell

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Background information. Fluoride is a well‐known G‐protein activator. Exposure of cultured cells to its derivatives results in actin cytoskeleton remodelling. Podosomes are actin‐based structures endowed with adhesion and matrix‐degradation functions. This study investigates actin cytoskeleton reorganization induced by fluoride in endothelial cells.Results. Treatment of cultured endothelial cells with sodium fluoride (NaF) results in a rapid and potent stimulation of podosome formation. Furthermore, we show that Cdc42 (cell‐division cycle 42), Rac1 and RhoA activities are stimulated in NaF‐treated cells. However, podosome assembly is dependent on Cdc42 and Rac1, but not RhoA. Although the sole activation of Cdc42 is sufficient to induce individual podosomes, a balance between RhoGTPase activities regulates podosome formation in response to NaF, which in this case are often found in groups or rosettes. As in other models, podosome formation in endothelial cells exposed to NaF also involves Src. Finally, we demonstrate that NaF‐induced podosomes are fully competent for matrix protein degradation.Conclusions. Taken together, our findings establish NaF as a novel inducer of podosomes in endothelial cells in vitro.

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Section: Discussionsupporting

confidence: 78%

Sodium fluoride induces podosome formation in endothelial cells

Tatin

Grise

Reuzeau

et al. 2010

Biology of the Cell

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“…It was recently shown that SRC-induced podosomes in human umbilical vein endothelial cells display gelatinolytic activity due to MMP2, activated by MT1-MMP (67). In addition, when formation of podosomes was compromised by addition of PP2, an inhibitor of Src as well as podosome formation, MT1-MMP-driven matrix degradation was inhibited, suggesting that SRC kinase is an upstream regulator of MT1-MMP-dependent matrix degradation in podosomes (68). The current data provide support for a mechanistic link between collagen adhesion, integrin clustering, and integrinmediated signaling via Src kinases to induce expression of EGR1, resulting in transcriptional activation of the MT1-MMP promoter and subsequent MT1-MMP-catalyzed intra-peritoneal invasion.…”

Section: Discussionmentioning

confidence: 99%

Microenvironmental Regulation of Membrane Type 1 Matrix Metalloproteinase Activity in Ovarian Carcinoma Cells via Collagen-induced EGR1 Expression

Barbolina

Adley

Ariztia

et al. 2007

Journal of Biological Chemistry

122

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Late stage ovarian cancer is characterized by disseminated intraperitoneal metastasis as secondary lesions anchor in the type I and III collagen-rich submesothelial matrix. Ovarian carcinoma cells preferentially adhere to interstitial collagen, and collagen-induced integrin clustering up-regulates the expression of the transmembrane collagenase membrane type 1 matrix metalloproteinase (MT1-MMP). Collagenolytic activity is important in intraperitoneal metastasis, potentiating invasion through the mesothelial cell layer and colonization of the submesothelial collagen-rich matrix. The objective of this study was to elucidate a potential mechanistic link between collagen adhesion and MT1-MMP expression. Our results indicate that culturing cells on three-dimensional collagen gels, but not thin layer collagen or synthetic threedimensional hydrogels, results in rapid induction of the transcription factor EGR1. Integrin signaling through a SRC kinasedependent pathway is necessary for EGR1 induction. Silencing of EGR1 expression using small interfering RNA abrogated collagen-induced MT1-MMP expression and inhibited cellular invasion of three-dimensional collagen gels. These data support a model for intraperitoneal metastasis wherein collagen adhesion and clustering of collagen binding integrins activates integrin-mediated signaling via SRC kinases to induce expression of EGR1, resulting in transcriptional activation of the MT1-MMP promoter and subsequent MT1-MMP-catalyzed collagen invasion. This model highlights the role of unique interactions between ovarian carcinoma cells and interstitial collagens in the ovarian tumor microenvironment in inducing gene expression changes that potentiate intraperitoneal metastatic progression.Epithelial ovarian carcinoma is the leading cause of death from gynecologic malignancy (1), due primarily to the fact that the majority of patients are diagnosed at late stage (III and IV) when metastasis has already occurred. Approximately 10% of all epithelial ovarian carcinomas are hereditary and may be facilitated by gene mutations, whereas the remaining 90% are sporadic (2-6). Tumors are thought to arise from the single cell layer of the ovarian epithelium and metastasis occurs via direct extension into the peritoneal cavity, where shed cells from the primary tumor are found as a component of malignant ascites. Secondary tumors arise as a consequence of CD44-and integrin-mediated intra-peritoneal adhesion and localized invasion into the interstitial collagen-rich submesothelial matrix. Proteolytic activity is important at multiple stages in intraperitoneal metastasis, including disruption of cell-cell interactions, migration and invasion into the mesothelial cell layer, and the submesothelial matrix to anchor secondary lesions, and for subsequent tumor-mediated angiogenesis (7).Multiple studies have shown that microenvironmental contacts with stromal cells or extracellular matrix elements may play a major role in tumor progression by inducing epigenetic changes in transformed cells (8,9). Met...

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“…Nonetheless, a number of proteins that are important for invadopodia formation and for the execution of EMT have been identified, strongly suggesting that invadopodia formation could be involved in EMT-driven cell invasion. Both EMT and invadopodia formation can be stimulated by various growth factors, including EGF, HGF, PDGF, and TGFβ [5,197,221]. The engagement of these growth factors leads to the activation of the non-receptor tyrosine kinase Src.…”

Section: Invadopodia and Their Role In Emtmentioning

confidence: 99%

EMT, the cytoskeleton, and cancer cell invasion

Yilmaz

Christofori

2009

Cancer Metastasis Rev

1,529

1,314

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The metastatic process, i.e. the dissemination of cancer cells throughout the body to seed secondary tumors at distant sites, requires cancer cells to leave the primary tumor and to acquire migratory and invasive capabilities. In a process of epithelial-mesenchymal transition (EMT), besides changing their adhesive repertoire, cancer cells employ developmental processes to gain migratory and invasive properties that involve a dramatic reorganization of the actin cytoskeleton and the concomitant formation of membrane protrusions required for invasive growth. The molecular processes underlying such cellular changes are still only poorly understood, and the various migratory organelles, including lamellipodia, filopodia, invadopodia and podosomes, still require a better functional and molecular characterization. Notably, direct experimental evidence linking the formation of migratory membrane protrusions and the process of EMT and tumor metastasis is still lacking. In this review, we have summarized recent novel insights into the molecular processes and players underlying EMT on one side and the formation of invasive membrane protrusions on the other side.

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Transforming Growth Factor β Induces Rosettes of Podosomes in Primary Aortic Endothelial Cells

Cited by 153 publications

References 62 publications

Sodium fluoride induces podosome formation in endothelial cells

Sodium fluoride induces podosome formation in endothelial cells

Microenvironmental Regulation of Membrane Type 1 Matrix Metalloproteinase Activity in Ovarian Carcinoma Cells via Collagen-induced EGR1 Expression

EMT, the cytoskeleton, and cancer cell invasion

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