References of "Deroanne, Christophe"
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See detailDynamics of Internalization and Recycling of the Pro-Metastatic Membrane Type 4-Matrix Metalloproteinase (MT4-MMP) in Breast Cancer Cells
Truong, Alice ULg; Yip, Cassandre ULg; PAYE, Alexandra ULg et al

in FEBS Journal (2016), 283(4), 704-22

MT4-MMP (MMP17) is a glycosylphosphatidyl inositol (GPI)-anchored membrane-type MMP expressed on the cell surface of human breast cancer cells. In triple negative breast cancer cells, MT4-MMP promotes ... [more ▼]

MT4-MMP (MMP17) is a glycosylphosphatidyl inositol (GPI)-anchored membrane-type MMP expressed on the cell surface of human breast cancer cells. In triple negative breast cancer cells, MT4-MMP promotes primary tumor growth and lung metastases. Although trafficking and internalization of the transmembrane MT1-MMP have been extensively investigated, little is known about the regulatory mechanisms of the GPI-anchored MT4-MMP. Here, we investigated the fate and cellular trafficking of MT4-MMP by analyzing its homophilic complex interactions, internalization and recycling dynamics compared to an inert form, MT4-MMP-E249A. Oligomeric and dimeric complexes were analyzed by co-transfection of cells with FLAG- or Myc-tagged MT4-MMP by reducing and non-reducing immunoblots and co-immunoprecipitation experiments. The trafficking of MT4-MMP was studied using an antibody feeding assay and confocal microscopy analysis or cell surface protein biotinylation and Western blot analysis. We demonstrate that MT4-MMP forms homophilic complexes at the cell surface, internalizes in early endosomes, and some of the enzyme is either auto-degraded or recycled to the cell surface. Our data indicate that MT4-MMP is internalized by the CLIC/GEEC pathway, a mechanism that differs from other MT-MMP members. Although MT4-MMP localizes with caveolin-1, MT4-MMP internalization was not affected by inhibitors of caveolin-1 or clathrin endocytosis pathways but was reduced by cdc42 or RhoA silencing with siRNA. We provide a new mechanistic insight into the regulatory mechanisms of MT4-MMP, which may have implications in the design of novel therapeutic strategies for metastatic breast cancer. This article is protected by copyright. All rights reserved. [less ▲]

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See detailDynamics of Internalization and Recycling of the pro-Metastatic Membrane Type 4-Matrix Metalloproteinase (MT4-MMP) in Breast Cancer cells
Truong, Alice ULg; Yip, Cassandre ULg; PAYE, Alexandra ULg et al

Poster (2015, October 26)

MT4-MMP (MMP17) is a glycosyl-phosphatidyl inositol-anchored membrane-type matrix metalloproteinase expressed at the cell surface of human breast cancer cells. In triple negative breast cancer, MT4-MMP ... [more ▼]

MT4-MMP (MMP17) is a glycosyl-phosphatidyl inositol-anchored membrane-type matrix metalloproteinase expressed at the cell surface of human breast cancer cells. In triple negative breast cancer, MT4-MMP promotes primary tumor growth and lung metastases. Recently, we demonstrated that EGFR activation and signaling are enhanced by MT4-MMP in a non-proteolytic dependent manner. While trafficking and internalization of EGFR was extensively investigated, little is known about MT4-MMP. Here, we investigated the dimerization, internalization and recycling dynamics of MT4-MMP and its mutated inactive form MT4-MMP-E249A. We demonstrate that MT4-MMP forms dimers and oligomers at the cell surface, a process that was not inhibited neither by broad-spectrum MMP inhibitors (GM6001 and BB94) nor TIMP-2. MT4-MMP is internalized in early endosomes from 10 minutes to 60 minutes. Once internalized, some amount of MT4-MMP is auto-degraded, whereas its inert form E249A was found intact. Large part of the internalized enzyme was recycled intact at the cell surface. By exploring its endocytosis, we found that MT4-MMP is internalized by the CLIC/GEEC pathway, a mechanism that differs from other MT-MMP members. Overall, we provided a new mechanistic insight on the regulatory mechanisms of MT4-MMP in human breast cancer cells. We also, highlighted unique features of MT4-MMP among membrane-associated MMPs, which may be useful for the design of novel therapeutic strategies for metastatic breast cancer. [less ▲]

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See detailLipin-1 regulates cancer cell phenotype and is a potential target to potentiate rapamycin treatment
Brohée, Laura ULg; Demine, Stéphane; Willems, Jérôme ULg et al

in Oncotarget (2015), 6(13), 11264-11280

Lipogenesis inhibition was reported to induce apoptosis and repress proliferation of cancer cells while barely affecting normal cells. Lipins exhibit dual function as enzymes catalyzing the ... [more ▼]

Lipogenesis inhibition was reported to induce apoptosis and repress proliferation of cancer cells while barely affecting normal cells. Lipins exhibit dual function as enzymes catalyzing the dephosphorylation of phosphatidic acid to diacylglycerol and as co-transcriptional regulators. Thus, they are able to regulate lipid homeostasis at several nodal points. Here, we show that lipin-1 is up-regulated in several cancer cell lines and overexpressed in 50 % of high grade prostate cancers. The proliferation of prostate and breast cancer cells, but not of non-tumorigenic cells, was repressed upon lipin-1 knock-down. Lipin-1 depletion also decreased cancer cell migration through RhoA activation. Lipin-1 silencing did not significantly affect global lipid synthesis but enhanced the cellular concentration of phosphatidic acid. In parallel, autophagy was induced while AKT and ribosomal protein S6 phosphorylation were repressed. We also observed a compensatory regulation between lipin-1 and lipin-2 and demonstrated that their co-silencing aggravates the phenotype induced by lipin-1 silencing alone. Most interestingly, lipin-1 depletion or lipins inhibition with propranolol sensitized cancer cells to rapamycin. These data indicate that lipin-1 controls main cellular processes involved in cancer progression and that its targeting, alone or in combination with other treatments, could open new avenues in anticancer therapy. [less ▲]

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See detailStudy of a new splice variant of Neuropilin-1: antagonistic functions in the regulation of cancer progression?
Hendricks, Céline ULg; Janssen, Lauriane; Delcombel, Romain et al

Poster (2015, April 22)

Neuropilin-1 (NRP1) is a transmembrane glycoprotein and a co-receptor for several growth factors, for example some variants of the Vascular Endothelial Growth Factor A (VEGF-A). It largely contributes to ... [more ▼]

Neuropilin-1 (NRP1) is a transmembrane glycoprotein and a co-receptor for several growth factors, for example some variants of the Vascular Endothelial Growth Factor A (VEGF-A). It largely contributes to the regulation of angiogenesis but also to cancer formation. NRP1 can be considered as a proteoglycan as glycosaminoglycans side chains can be added on serine 612. Currently, six splice variants of NRP1 have been described. An additional form was recently identified in our laboratory. Depending upon the cell types, it represents 20-30% of the total amount of NRP1. As compared to the full size NRP1 (NRP1-FS), 7 amino acids are deleted. As the missing sequence is located 2 amino acids downstream of the Ser612 required for glycosaminoglycans addition, this process could be somehow affected and the function of the protein could be modified. The glycosylation of NRP1-FS and -Δ7 was analyzed in different cells overexpressing each isoform. Western blotting analyses suggested that NRP1-Δ7 was less glycosylated than NRP1-FS. Prostate cancer cells (PC3) were engineered to express NRP1-FS or –Δ7 only in the presence of doxycycline. The migration of these cells was analyzed by scratch assay, with or without doxycycline in the medium. As compared to controls and to NRP1-FS-expressing cells, production of NRP1-Δ7 was linked to a reduction of cell migration. A DNA dosage showed that NRP1-FS enhanced cell proliferation, while NRP1-Δ7 reduced it. Tumor growth was assessed in vitro by a culture in soft agar. As compared to control conditions, expression of NRP1-FS by doxycycline increased colonies formation. By contrast, NRP1-Δ7 inhibited colonies number, suggesting an inhibition of tumorigenesis by this variant. As PC3 cells express basal level of endogenous NRP1, this suggests some competitive inhibition of NRP1 functions by NRP1-Δ7. Finally, the function of each variant was investigated in vivo in a model of injection in the flanks of nude mice of PC3 cells conditionally expressing NRP1-FS or -Δ7. As compared to the control, NRP1-FS increased tumor size and weight. By sharp contrast, the expression of NRP1-Δ7 was associated with a reduction of tumorigenicity. Cells with forced expression of NRP1-Δ7 also developed fewer blood vessels as compared to the control. These results suggest that NRP1-Δ7 have an antagonistic action on cancer formation and angiogenesis. [less ▲]

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See detailRhoGTPases as Key players in mammalian cell adaptation to microgravity.
Louis, Fiona; Deroanne, Christophe ULg; Nusgens-Richelle, Betty ULg et al

in BioMed Research International (2015)

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See detailRac1 GTPase silencing counteracts microgravity-induced effects on osteoblastic cells.
Guignandon, Alain; Fauré, Céline; Neutelings, Thibault et al

in FASEB Journal (2014), 28(9), 4077-4087

Bone cells exposed to real microgravity display alterations of their cytoskeleton and focal adhesions, two major mechanosensitive structures. These structures are controlled by small GTPases of the Ras ... [more ▼]

Bone cells exposed to real microgravity display alterations of their cytoskeleton and focal adhesions, two major mechanosensitive structures. These structures are controlled by small GTPases of the Ras homology (Rho) family. We investigated the effects of RhoA, Rac1, and Cdc42 modulation of osteoblastic cells under microgravity conditions. Human MG-63 osteoblast-like cells silenced for RhoGTPases were cultured in the automated Biobox bioreactor (European Space Agency) aboard the Foton M3 satellite and compared to replicate ground-based controls. The cells were fixed after 69 h of microgravity exposure for postflight analysis of focal contacts, F-actin polymerization, vascular endothelial growth factor (VEGF) expression, and matrix targeting. We found that RhoA silencing did not affect sensitivity to microgravity but that Rac1 and, to a lesser extent, Cdc42 abrogation was particularly efficient in counteracting the spaceflight-related reduction of the number of focal contacts [-50% in silenced, scrambled (SiScr) controls vs. -15% for SiRac1], the number of F-actin fibers (-60% in SiScr controls vs. -10% for SiRac1), and the depletion of matrix-bound VEGF (-40% in SiScr controls vs. -8% for SiRac1). Collectively, these data point out the role of the VEGF/Rho GTPase axis in mechanosensing and validate Rac1-mediated signaling pathways as potential targets for counteracting microgravity effects [less ▲]

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See detailCell Models Adapted to Real-Time Imaging of the Cytoskeleton Dynamics in Altered Gravity
Willems, Jérôme ULg; Deroanne, Christophe ULg; Colige, Alain ULg et al

in Microgravity Science and Technology (2014), 26(4), 257-270

Spatial and temporal regulation of cell phenotype by mechanical forces is a growing field of research in health sciences since these stimuli influence cellular functions, such as proliferation, migration ... [more ▼]

Spatial and temporal regulation of cell phenotype by mechanical forces is a growing field of research in health sciences since these stimuli influence cellular functions, such as proliferation, migration, differentiation and gene expression. In the context of the Fluolive project selected by the European Space Agency and aiming at evaluating the impact of gravity alterations on the cell phenotype, we have developed new bone-derived cell lines adapted for live-cell imaging of the cytoskeleton. Osteoblastic cells derived from human osteosarcomas were used as experimental models. U2-OS and SaoS-2 cells stably expressing TagGFP2- β-actin and mCherry- α-tubulin were established and single-cell clonal cultures were characterized in terms of recombinant proteins production and localization, fluorescence intensity, cell proliferation and migration rates. Living fluorescently-tagged cell lines allow real-time fluorescence microscopy of the cytoskeleton dynamics without bleaching and without alteration of cell morphology. U2-OS and SaoS-2 TagGFP2- β-actin and mCherry- α-tubulin clones will be used to monitor the effect of mechanical forces in models of altered gravity on Earth and possibly on the ISS. © 2014, Springer Science+Business Media Dordrecht. [less ▲]

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See detailHuman papillomavirus entry into NK cells requires CD16 expression and triggers cytotoxic activity and cytokine secretion
Renoux, Virginie; Bisig, Bettina; Langers, Inge ULg et al

Poster (2013, May)

Human papillomavirus (HPV) infections account for more than 50% of infection-linked cancers in women worldwide. The immune system controls, at least partially, viral infection and around 90% of HPV ... [more ▼]

Human papillomavirus (HPV) infections account for more than 50% of infection-linked cancers in women worldwide. The immune system controls, at least partially, viral infection and around 90% of HPV-infected women clear the virus within two years. However, it remains unclear which immune cells are implicated in this process and no study has evaluated the direct interaction between HPVs and NK cells, a key player in host resistance to viruses and tumors. We demonstrated an NK-cell infiltration in HPV- associated preneoplastic cervical lesions. Since HPVs cannot grow in vitro, virus-like particles (VLPs) were used as a model for studying the NK-cell response against the virus. Interestingly, NK cells displayed higher cytotoxic activity and cytokine production (TNF-a and IFN-g) in the presence of HPV-VLPs. Using flow cytometry and microscopy, we observed that NK-cell stimulation was linked to rapid VLP entry into these cells by macropinocytosis. Using CD16+ and CD16- NK-cell lines and a CD16-blocking antibody, we demonstrated that CD16 is necessary for HPV–VLP internalization, as well as for degranulation and cytokine production. Thus, we show for the first time that NK cells interact with HPVs and can participate in the immune response against HPV-induced lesions. [less ▲]

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See detailEmerging pathogenic mechanisms in human myxomatous mitral valve: lessons from past and novel data.
Hulin, Alexia; Deroanne, Christophe ULg; Lambert, Charles ULg et al

in Cardiovascular Pathology (2013), 22

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See detailPP2A regulatory subunit Balpha controls endothelial contractility and vessel lumen integrity via regulation of HDAC7.
Martin, Maud ULg; Geudens, Ilse; Bruyr, Jonathan et al

in EMBO Journal (2013)

To supply tissues with nutrients and oxygen, the cardiovascular system forms a seamless, hierarchically branched, network of lumenized tubes. Here, we show that maintenance of patent vessel lumens ... [more ▼]

To supply tissues with nutrients and oxygen, the cardiovascular system forms a seamless, hierarchically branched, network of lumenized tubes. Here, we show that maintenance of patent vessel lumens requires the Balpha regulatory subunit of protein phosphatase 2A (PP2A). Deficiency of Balpha in zebrafish precludes vascular lumen stabilization resulting in perfusion defects. Similarly, inactivation of PP2A-Balpha in cultured ECs induces tubulogenesis failure due to alteration of cytoskeleton dynamics, actomyosin contractility and maturation of cell-extracellular matrix (ECM) contacts. Mechanistically, we show that PP2A-Balpha controls the activity of HDAC7, an essential transcriptional regulator of vascular stability. In the absence of PP2A-Balpha, transcriptional repression by HDAC7 is abrogated leading to enhanced expression of the cytoskeleton adaptor protein ArgBP2. ArgBP2 hyperactivates RhoA causing inadequate rearrangements of the EC actomyosin cytoskeleton. This study unravels the first specific role for a PP2A holoenzyme in development: the PP2A-Balpha/HDAC7/ArgBP2 axis maintains vascular lumens by balancing endothelial cytoskeletal dynamics and cell-matrix adhesion. [less ▲]

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See detailNew prospects in the roles of the C-terminal domains of VEGF-A and their cooperation for ligand binding, cellular signaling and vessels formation.
Delcombel, Romain ULg; Janssen, Lauriane ULg; Vassy, Roger et al

in Angiogenesis (2013), 16(2), 353-71

VEGF-A is a crucial growth factor for blood vessel homeostasis and pathological angiogenesis. Due to alternative splicing of its pre-mRNA, VEGF-A is produced under several isoforms characterized by the ... [more ▼]

VEGF-A is a crucial growth factor for blood vessel homeostasis and pathological angiogenesis. Due to alternative splicing of its pre-mRNA, VEGF-A is produced under several isoforms characterized by the combination of their C-terminal domains, which determines their respective structure, availability and affinity for co-receptors. As controversies still exist about the specific roles of these exon-encoded domains, we systematically compared the properties of eight natural and artificial variants containing the domains encoded by exons 1-4 and various combinations of the domains encoded by exons 5, 7 and 8a or 8b. All the variants (VEGF(111)a, VEGF(111)b, VEGF(121)a, VEGF(121)b, VEGF(155)a, VEGF(155)b, VEGF(165)a, VEGF(165)b) have a similar affinity for VEGF-R2, as determined by Surface plasmon resonance analyses. They strongly differ however in terms of binding to neuropilin-1 and heparin/heparan sulfate proteoglycans. Data indicate that the 6 amino acids encoded by exon 8a must be present and cooperate with those of exons 5 or 7 for efficient binding, which was confirmed in cell culture models. We further showed that VEGF(165)b has inhibitory effects in vitro, as previously reported, but that the shortest VEGF variant possessing also the 6 amino acids encoded by exon 8b (VEGF(111)b) is remarkably proangiogenic, demonstrating the critical importance of domain interactions for defining the VEGF properties. The number, size and localization of newly formed blood vessels in a model of tumour angiogenesis strongly depend also on the C-terminal domain composition, suggesting that association of several VEGF isoforms may be more efficient for treating ischemic diseases than the use of any single variant. [less ▲]

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See detailOncogenic human papillomavirus could directly interact with Natural Killer cells
Renoux, Virginie; Bastin, Renaud ULg; Boniver, Jacques ULg et al

Poster (2012, December 10)

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See detailOncogenic human papillomavirus could directly interact with Natural Killer cells
Renoux, Virginie; Bastin, Renaud ULg; Boniver, Jacques ULg et al

Poster (2012, June 22)

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See detailOncogenic human papillomavirus could directly interact with Natural Killer cells
Renoux, Virginie; Bastin, Renaud ULg; Boniver, Jacques ULg et al

Poster (2012, May 04)

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See detailRho proteins crosstalk via RhoGDIalpha
Stultiens, Audrey ULg; HO, Thi Thanh Giang ULg; Nusgens, Betty ULg et al

in Communicative & Integrative Biology (2012), 5(1), 99-101

Detailed reference viewed: 48 (19 ULg)