Differential functions of tissue factor in the trans-activation of cellular signalling pathways

Ettelaie, Camille; Li, Chao; Collier, Mary E.W.; Pradier, Amandine; Frentzou, Georgia A.; Wood, Charlotte; Chetter, Ian; McCollum, P. T.; Bruckdorfer, K. Richard; James, N. J.

doi:10.1016/j.atherosclerosis.2006.10.010

Cited by 15 publications

(17 citation statements)

References 56 publications

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“…This indicates that the transfer of microparticle TF from stromal cells to breast cancer cells may directly influence the breast cancer cells. The ability of exogenous rTF to activate the MAPK cell signaling pathway has been shown previously (11) and was also confirmed here. Furthermore, activation of the ERK1/2 MAPK signaling pathway has been implicated previously in the down-regulation of ERa expression (12,13).…”

Section: Discussionsupporting

confidence: 67%

“…Neutralization of the labeled rTF using a polyclonal anti-TF antibody or competition with excess unlabeled rTF abolished the binding of fluoresceinlabeled rTF (Table 1). We have shown previously that rTF binds to the surface of endothelial cells (11,14), which possibly occurs through binding to putative cell receptors capable of interacting with TF (16). Furthermore, rTF appeared to be focused at particular points on the cell membrane as reported previously for endogenous TF (17), suggesting an interaction with specific cell surface proteins also localized to these points.…”

Section: Mol Cancer Res 2008;6(12) December 2008mentioning

confidence: 64%

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Influence of Exogenous Tissue Factor on Estrogen Receptorα Expression in Breast Cancer Cells: Involvement of β1-Integrin, PAR2, and Mitogen-Activated Protein Kinase Activation

Collier

Ettelaie

2008

Molecular Cancer Research

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Increased expression of tissue factor (TF) has been associated with invasive forms of breast cancer. Conversely, the loss of estrogen receptor A (ERA) is associated with increased cell invasiveness. We have examined the influence of exogenous truncated recombinant TF (rTF) on ERA expression and cell invasiveness and investigated the mechanism of rTF signaling. The influence of rTF on ERA expression in MCF-7 and T47D cell lines was investigated using reverse transcription-PCR and ELISA. Cell invasion was measured using Boyden chamber-based invasion assays. Additionally, the interaction of fluorescein-labeled rTF with the surface of MCF-7 cells and particularly with B 1 -integrin was examined. Treatment of cells with rTF resulted in the downregulation of ERA mRNA and protein over 24 h, which required B 1 -integrin and involved the mitogen-activated protein kinase pathway but did not require PAR2 activation. The addition of rTF reduced estradiol-mediated cell proliferation as well as increased cell invasiveness requiring both PAR2 and B 1 -integrin activation. Fluorescein-labeled rTF was shown to bind to the surface of MCF-7 cells within 5 min and peaked at 15 min. The bound rTF colocalized with cellular B 1 -integrin and was disrupted in the presence of excess unlabeled rTF and an anti-B 1 polyclonal antibody. Finally, affinity purification of B 1 -integrin using rTF-conjugated agarose showed a requirement for the presence of divalent cations but not factor VIIa. The results indicate that rTF is capable of down-regulating ERA expression in breast cancer cells, resulting in decreases in estrogen-mediated cell proliferation and increased invasiveness. Furthermore, the mechanisms by which rTF induces these changes involve both PAR2 and B 1 -integrin.

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Section: Discussionsupporting

confidence: 67%

Section: Mol Cancer Res 2008;6(12) December 2008mentioning

confidence: 64%

Influence of Exogenous Tissue Factor on Estrogen Receptorα Expression in Breast Cancer Cells: Involvement of β1-Integrin, PAR2, and Mitogen-Activated Protein Kinase Activation

Collier

Ettelaie

2008

Molecular Cancer Research

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“…Multiple studies now indicate that TF⅐FVIIa⅐Xa complexes initiates signal transduction, resulting in the activation of a number of pathways that shape the microenvironment of the tumor (25,26). Interestingly, our results demonstrated that the PDZ scaffold protein MDA-9/syntenin forms a signaling complex with Src that requires exogeneous rFVIIa and FX.…”

Section: Discussionmentioning

confidence: 54%

“…3D and data not shown). Activation of the NF-B pathway is another key feature of TF⅐FVIIa⅐FXa-mediated regulation of gene expression (26). Treatment of serumstarved melanoma cells, T1P26 and c8161, with rFVIIa ϩ FX significantly increased the transcriptional activity of the NF-B-responsive promoter compared with untreated cells (Fig.…”

Section: Fviia⅐xa-induced Mda-9/syntenin Expression Signals Through Pmentioning

confidence: 99%

“…A number of gain-and loss-of-function studies have shown that genetic modulation of TF promotes tumor cell invasion/migration and metastasis in vivo (20 -22). Current studies indicate that the ternary TF⅐FVIIa⅐Xa complex, efficiently signals through PAR-1 or PAR-2 in a FXa-dependent manner (23,24) and cross-talks with several important cellular signaling pathways, including MAPK pathway, Src family tyrosine kinases, and NFB members (25,26). Considering these many provocative findings, we have presently investigated the possible role of TF⅐FVIIa and the induced signaling pathways in regulation of MDA-9/syntenin expression.…”

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confidence: 99%

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MDA-9/Syntenin Is Essential for Factor VIIa-induced Signaling, Migration, and Metastasis in Melanoma Cells

Aissaoui

Prévost

Boucharaba

et al. 2015

Journal of Biological Chemistry

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Background: MDA-9/syntenin and tissue factor (TF) are overexpressed in most types of human cancer. Results: Induction of MDA-9/syntenin in melanoma involves the binding of FVIIa and FX to TF on the cell surface, which initiates a signaling circuit essential for cell motility and metastasis of melanoma. Conclusion: MDA-9/syntenin is an important TF-regulated gene. Significance: Targeting TF-mediated MDA-9/syntenin may represent a novel therapeutic strategy for eliminating cancer.

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Loss of DPP4 activity is related to a prothrombogenic status of endothelial cells: implications for the coronary microvasculature of myocardial infarction patients

Krijnen

Hahn

Kholová³

et al. 2011

Basic Res Cardiol

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Pro-coagulant and pro-inflammatory intramyocardial (micro)vasculature plays an important role in acute myocardial infarction (AMI). Currently, inhibition of serine protease dipeptidyl peptidase 4 (DPP4) receives a lot of interest as an anti-hyperglycemic therapy in type 2 diabetes patients. However, DPP4 also possesses anti-thrombotic properties and may behave as an immobilized anti-coagulant on endothelial cells. Here, we studied the expression and activity of endothelial DPP4 in human myocardial infarction in relation to a prothrombogenic endothelial phenotype. Using (immuno)histochemistry, DPP4 expression and activity were found on the endothelium of intramyocardial blood vessels in autopsied control hearts (n = 9). Within the infarction area of AMI patients (n = 73), this DPP4 expression and activity were significantly decreased, coinciding with an increase in Tissue Factor expression. In primary human umbilical vein endothelial cells (HUVECs), Western blot analysis and digital imaging fluorescence microscopy revealed that DPP4 expression was strongly decreased after metabolic inhibition, also coinciding with Tissue Factor upregulation. Interestingly, inhibition of DPP4 activity with diprotin A also enhanced the amount of Tissue Factor encountered and induced the adherence of platelets under flow conditions. Ischemia induces loss of coronary microvascular endothelial DPP4 expression and increased Tissue Factor expression in AMI as well as in vitro in HUVECs. Our data suggest that the loss of DPP4 activity affects the anti-thrombogenic nature of the endothelium.

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Differential functions of tissue factor in the trans-activation of cellular signalling pathways

Cited by 15 publications

References 56 publications

Influence of Exogenous Tissue Factor on Estrogen Receptorα Expression in Breast Cancer Cells: Involvement of β1-Integrin, PAR2, and Mitogen-Activated Protein Kinase Activation

Influence of Exogenous Tissue Factor on Estrogen Receptorα Expression in Breast Cancer Cells: Involvement of β1-Integrin, PAR2, and Mitogen-Activated Protein Kinase Activation

MDA-9/Syntenin Is Essential for Factor VIIa-induced Signaling, Migration, and Metastasis in Melanoma Cells

Loss of DPP4 activity is related to a prothrombogenic status of endothelial cells: implications for the coronary microvasculature of myocardial infarction patients

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