References of "Thiry, Marc"
     in
Bookmark and Share    
Full Text
Peer Reviewed
See detailMyoferlin is a novel exosomal protein and functional regulator of cancer-derived exosomes
Blomme, Arnaud; Fahmy, Karim; Peulen, Olivier ULg et al

in Oncotarget (2016)

Exosomes are communication mediators participating in the intercellular exchange of proteins, metabolites and nucleic acids. Recent studies have demonstrated that exosomes are characterized by a unique ... [more ▼]

Exosomes are communication mediators participating in the intercellular exchange of proteins, metabolites and nucleic acids. Recent studies have demonstrated that exosomes are characterized by a unique proteomic composition that is distinct from the cellular one. The mechanisms responsible for determining the proteome content of the exosomes remain however obscure. In the current study we employ ultrastructural approach to validate a novel exosomal protein myoferlin. This is a multiple C2-domain containing protein, known for its conserved physiological function in endocytosis and vesicle fusion biology. Emerging studies demonstrate that myoferlin is frequently overexpressed in cancer, where it promotes cancer cell migration and invasion. Our data expand these ndings by showing that myoferlin is a general component of cancer cell derived exosomes from different breast and pancreatic cancer cell lines. Using proteomic analysis, we demonstrate for the rst time that myoferlin depletion in cancer cells leads to a signi cantly modulated exosomal protein load. Such myoferlin-depleted exosomes were also functionally de cient as shown by their reduced capacity to transfer nucleic acids to human endothelial cells (HUVEC). Beyond this, myoferlin-depleted cancer exosomes also had a signi cantly reduced ability to induce migration and proliferation of HUVEC. The present study highlights myoferlin as a new functional player in exosome biology, calling for novel strategies to target this emerging oncogene in human cancer. [less ▲]

Detailed reference viewed: 11 (1 ULg)
Full Text
Peer Reviewed
See detailMyoferlin regulates cellular lipid metabolism and promotes metastases in triple-negative breast cancer
Blomme, Arnaud; Costanza, Brunella ULg; De Tullio, Pascal ULg et al

in Oncogene (2016)

Myoferlin is a multiple C2-domain-containing protein that regulates membrane repair, tyrosine kinase receptor function and endocytosis in myoblasts and endothelial cells. Recently it has been reported as ... [more ▼]

Myoferlin is a multiple C2-domain-containing protein that regulates membrane repair, tyrosine kinase receptor function and endocytosis in myoblasts and endothelial cells. Recently it has been reported as overexpressed in several cancers and shown to contribute to proliferation, migration and invasion of cancer cells. We have previously demonstrated that myoferlin regulates epidermal growth factor receptor activity in breast cancer. In the current study, we report a consistent overexpression of myoferlin in triple-negative breast cancer cells (TNBC) over cells originating from other breast cancer subtypes. Using a combination of proteomics, metabolomics and electron microscopy, we demonstrate that myoferlin depletion results in marked alteration of endosomal system and metabolism. Mechanistically, myoferlin depletion caused impaired vesicle traffic that led to a misbalance of saturated/unsaturated fatty acids. This provoked mitochondrial dysfunction in TNBC cells. As a consequence of the major metabolic stress, TNBC cells rapidly triggered AMP activated protein kinase-mediated metabolic reprogramming to glycolysis. This reduced their ability to balance between oxidative phosphorylation and glycolysis, rendering TNBC cells metabolically inflexible, and more sensitive to metabolic drug targeting in vitro. In line with this, our in vivo findings demonstrated a significantly reduced capacity of myoferlin-deficient TNBC cells to metastasise to lungs. The significance of this observation was further supported by clinical data, showing that TNBC patients whose tumors overexpress myoferlin have worst distant metastasis-free and overall survivals. This novel insight into myoferlin function establishes an important link between vesicle traffic, cancer metabolism and progression, offering new diagnostic and therapeutic concepts to develop treatments for TNBC patients. [less ▲]

Detailed reference viewed: 12 (4 ULg)
Full Text
See detailBiologie cellulaire: exercices et méthodes
Thiry, Marc ULg; Rigo, Pierre ULg; Racano, Sandra

Book published by Dunod - 2ème édition (2016)

Cet ouvrage propose aux étudiants des premières années d’études supérieures une méthode progressive et conviviale pour comprendre et appliquer les concepts fondamentaux de la biologie cellulaire. À la ... [more ▼]

Cet ouvrage propose aux étudiants des premières années d’études supérieures une méthode progressive et conviviale pour comprendre et appliquer les concepts fondamentaux de la biologie cellulaire. À la suite de rappels de cours, sous forme de fiches, chaque chapitre propose des exercices de difficulté croissante pour s’évaluer : QCM, questions Vrai/Faux et exercices de synthèse. Les corrigés détaillés mettent en évidence la méthodologie. Des ressources numériqes avec des exercices d’entraînement supplémentaires complètent l’ouvrage. Cette nouvelle édition, actualisée, s'enrichit de nouveaux QCM, Vrai/Faux et exercices. [less ▲]

Detailed reference viewed: 126 (18 ULg)
Full Text
See detailBiologie moléculaire: exercices et méthodes
Thiry, Marc ULg; Bourmeyster, Nicolas; Dommes, Jacques ULg et al

Book published by Dunod (2016)

Cet ouvrage constitue une méthode progressive et efficace pour comprendre et appliquer les concepts fondamentaux de la biologie moléculaire. Il propose : des rappels de cours sous forme de fiches, des ... [more ▼]

Cet ouvrage constitue une méthode progressive et efficace pour comprendre et appliquer les concepts fondamentaux de la biologie moléculaire. Il propose : des rappels de cours sous forme de fiches, des exercices pour s'évaluer (QCM, questions Vrai/Faux, exercices de synthèse...), des corrigés détaillés. Des exercices d’entraînement supplémentaires sont téléchargeables sur le site dunod.com. [less ▲]

Detailed reference viewed: 53 (11 ULg)
Full Text
See detailRole of vimentin in the hearing organ
Renauld, Justine ULg; Francart, Marie-Emilie ULg; Thelen, Nicolas ULg et al

Conference (2016, January 25)

Detailed reference viewed: 46 (5 ULg)
Full Text
Peer Reviewed
See detailLung-resident eosinophils represent a distinct regulatory eosinophil subset
Mesnil, Claire ULg; Raulier, Stéfanie ULg; Paulissen, G et al

in Journal of Clinical Investigation (2016), 126(9), 3275-3295

Increases in eosinophil numbers are associated with infection and allergic diseases, including asthma, but there is also evidence that eosinophils contribute to homeostatic immune processes. In mice, the ... [more ▼]

Increases in eosinophil numbers are associated with infection and allergic diseases, including asthma, but there is also evidence that eosinophils contribute to homeostatic immune processes. In mice, the normal lung contains resident eosinophils (rEos), but their function has not been characterized. Here, we have reported that steady-state pulmonary rEos are IL-5–independent parenchymal Siglec-FintCD62L+CD101lo cells with a ring-shaped nucleus. During house dust mite–induced airway allergy, rEos features remained unchanged, and rEos were accompanied by recruited inflammatory eosinophils (iEos), which were defined as IL-5–dependent peribronchial Siglec-FhiCD62L–CD101hi cells with a segmented nucleus. Gene expression analyses revealed a more regulatory profile for rEos than for iEos, and correspondingly, mice lacking lung rEos showed an increase in Th2 cell responses to inhaled allergens. Such elevation of Th2 responses was linked to the ability of rEos, but not iEos, to inhibit the maturation, and therefore the pro-Th2 function, of allergen-loaded DCs. Finally, we determined that the parenchymal rEos found in nonasthmatic human lungs (Siglec-8+CD62L+IL-3Rlo cells) were phenotypically distinct from the iEos isolated from the sputa of eosinophilic asthmatic patients (Siglec-8+CD62LloIL-3Rhi cells), suggesting that our findings in mice are relevant to humans. In conclusion, our data define lung rEos as a distinct eosinophil subset with key homeostatic functions. [less ▲]

Detailed reference viewed: 26 (16 ULg)
Full Text
Peer Reviewed
See detailMyoferlin plays a key role in VEGFA secretion and impacts tumor-associated angiogenesis in human pancreas cancer
Fahmy, Karim ULg; Gonzalez, Arnaud ULg; Arafa, Mohammad et al

in International Journal of Cancer = Journal International du Cancer (2016), 138

Pancreatic ductal adenocarcinoma is one of the most deadly forms of cancers with no satisfactory treatment to date. Recent studies have identified myoferlin, a ferlin family member, in human pancreas ... [more ▼]

Pancreatic ductal adenocarcinoma is one of the most deadly forms of cancers with no satisfactory treatment to date. Recent studies have identified myoferlin, a ferlin family member, in human pancreas adenocarcinoma where its expression was associated to a bad prognosis. However, the function of myoferlin in pancreas adenocarcinoma has not been reported. In other cell types, myoferlin is involved in several key plasma membrane processes such as fusion, repair, endocytosis and tyrosine kinase receptor activity. In this study, we showed that myoferlin silencing in BxPC-3 human pancreatic cancer cells resulted in the inhibition of cell proliferation in vitro and in a significant reduction of the tumor volume in chick chorioallantoic membrane assay. In addition to be smaller, the tumors formed by the myoferlin-silenced cells showed a marked absence of functional blood vessels. We further demonstrated that this effect was due, at least in part, to an inhibition of VEGFA secretion by BxPC-3 myoferlin-silenced cells. Using immunofluorescence and electron microscopy, we linked the decreased VEGFA secretion to an impairment of VEGFA exocytosis. The clinical relevance of our results was further strengthened by a significant correlation between myoferlin expression in a series of human pancreatic malignant lesions and their angiogenic status evaluated by the determination of the blood vessel density. [less ▲]

Detailed reference viewed: 108 (31 ULg)
Full Text
Peer Reviewed
See detailExpanding the clinical and mutational spectrum of the Ehlers-Danlos syndrome Dermatosparaxis.
Van Damme, Tim; Colige, Alain ULg; Syx, Delfien et al

in Genetics in Medicine : Official Journal of the American College of Medical Genetics (2016)

Detailed reference viewed: 126 (4 ULg)
See detailChanges in the structure and the composition of microtubules within supporting cells of the organ of hearing during development.
Renauld, Justine ULg; Freeman, Stephen ULg; Thelen, Nicolas ULg et al

Poster (2016)

The auditory organ is a highly specialized structure composed by specific cellular types. The sensory cells are characterized by stereocilia at their apex and are necessary for the sound perception. These ... [more ▼]

The auditory organ is a highly specialized structure composed by specific cellular types. The sensory cells are characterized by stereocilia at their apex and are necessary for the sound perception. These cells are supported by supporting cells which contain up to 3000 microtubules and are formed by 15protofilaments (15pf) instead of the canonical 13, a unique fact among vertebrates. It was shown that a β-tubulin isoform can specify the microtubule architecture, such as the expression of the Moth β2 in the Drosophila testes imposed the 16pf structure on the corresponding subset of Drosophila microtubules, which normally contain 13pf. To determine the role of these tubulins in the auditory organ and their possible involvement in the formation of the unusual 15pf microtubules of supporting cells, we studied the spatiotemporal localization of five -tubulin isotypes (β1 to 5) as well as acetyl-α-tubulin within the hearing organ during development in rodents. By using confocal microscopy, we showed that with the exception of the β3-tubulin isoform that was specific to nerve fibres, all the different β-tubulin isoforms and acetyl-α-tubulin were mainly present in the supporting cells. Contrary to β1-4-tubulins, we also found that the β5-tubulin isoform appeared only at a key stage of the postnatal development. By using transmission electron microscopy, we examined the fine structure of microtubules at an early and a late postnatal stage. Our TEM study indicated that these cells are composed by 13pf microtubules at P2, but by 15pf microtubules at P25. We revealed further that this developmental stage coincide with the formation of two separate bundles of microtubules from a unique one in these supporting cells. In conclusion, the architecture and composition of microtubules present in the supporting cells change during development of the organ of Corti. Further experiments are now required to determine if these changes are related to the appearance of β5-tubulin. [less ▲]

Detailed reference viewed: 64 (6 ULg)
Full Text
Peer Reviewed
See detailTissue factor induced by epithelial-mesenchymal transition triggers a pro-coagulant state that drives metastasis of circulating tumor cells.
Bourcy, Morgane ULg; Suarez-Carmona, Meggy ULg; Lambert, Justine ULg et al

in Cancer Research (2016)

Epithelial-mesenchymal transition (EMT) is prominent in circulating tumor cells (CTC), but how it influences metastatic spread in this setting is obscure. Insofar as blood provides a specific ... [more ▼]

Epithelial-mesenchymal transition (EMT) is prominent in circulating tumor cells (CTC), but how it influences metastatic spread in this setting is obscure. Insofar as blood provides a specific microenvironment for tumor cells, we explored a potential link between EMT and coagulation that may provide EMT-positive CTC with enhanced colonizing properties. Here we report that EMT induces tissue factor (TF), a major cell-associated initiator of coagulation and related pro-coagulant properties in the blood. TF blockade by antibody or shRNA diminished the pro-coagulant activity of EMT-positive cells, confirming a functional role for TF in these processes. Silencing the EMT transcription factor ZEB1 inhibited both EMT-associated TF expression and coagulant activity, further strengthening the link between EMT and coagulation. Accordingly, EMT-positive cells exhibited a higher persistance/survival in the lungs of mice colonized after intravenous injection, a feature diminished by TF or ZEB1 silencing. In tumor cells with limited metastatic capability, enforcing expression of the EMT transcription factor Snail increased TF, coagulant properties and early metastasis. Clinically, we identified a subpopulation of CTC expressing vimentin and TF in the blood of metastatic breast cancer patients consistent with our observations. Overall, our findings define a novel EMT-TF regulatory axis which triggers local activation of coagulation pathways to support metastatic colonization of EMT-positive CTC. [less ▲]

Detailed reference viewed: 56 (22 ULg)
Full Text
Peer Reviewed
See detailMelanoma antigen-D2: a nucleolar protein undergoing delocalization during cell cycle and after cellular stress
Pirlot, Céline ULg; Thiry, Marc ULg; Trussart, Charlotte ULg et al

in BBA Molecular Cell Research (2016), 1853(3), 581-595

Detailed reference viewed: 17 (6 ULg)
Full Text
Peer Reviewed
See detailStudy of intact virus-like particles of human papillomavirus by capillary electrophoresis
Bettonville, Virginie ULg; Nicol, Jérôme ULg; Thelen, Nicolas ULg et al

in Electrophoresis (2016), 37

Virus-like particles of human papillomavirus (HPV-VLP), resulting from the self-assembly of the capsid proteins (L1 or L1 and L2), have been widely used to study HPV as they are similar to the native ... [more ▼]

Virus-like particles of human papillomavirus (HPV-VLP), resulting from the self-assembly of the capsid proteins (L1 or L1 and L2), have been widely used to study HPV as they are similar to the native virion. Moreover, two prophylactic vaccines, Gardasil® and Cervarix®, are based on HPV-VLP L1. Analytical techniques currently used to characterize HPV-VLP, such as SDS-PAGE, Western blot, ELISA, are time-consuming and semi-quantitative. In this study, capillary electrophoresis (CE) was evaluated for the analysis of intact HPV16-VLP. The usefulness of capillary inner wall coating as well as various BGEs, pH and detergent additives were investigated. Reproducible HPV-VLP analysis in CE was achieved using poly(ethylene oxide) coated capillary and a BGE containing high salt concentration and low SDS concentration. The developed method enables HPV-VLP detection in less than 10 min (migration times RSD : 1.6 %). The identity of HPV-VLP peak was confirmed by comparison with a sample obtained from a wild-type baculovirus and with VLP-based vaccine, Gardasil®, after adjuvant dissolution. Finally, we applied the developed methodology to VLP-based vaccines, demonstrating that CE could be successfully used for vaccine quality control. [less ▲]

Detailed reference viewed: 77 (22 ULg)
See detailMelanoma antigen D2, a substrate of ATM, is a nucleolar protein that shuttles with cell cycle and cellular stress.
Pirlot, Céline; Thiry, Marc ULg; Trussart, Charlotte ULg et al

Poster (2015, November 03)

ATM coordinates numerous facets of the highly regulated DDR network. In order to identify new ATM substrates we have performed a yeast two hybrid experiment with HEAT domains of ATM and an HeLa cDNA ... [more ▼]

ATM coordinates numerous facets of the highly regulated DDR network. In order to identify new ATM substrates we have performed a yeast two hybrid experiment with HEAT domains of ATM and an HeLa cDNA library. Melanoma antigen D2 (MAGED2) was one of the interacting proteins identified in this screen. MAGED2 belongs to the type II Melanoma AntiGEn (MAGE) family. MAGE homology domain, shared by all MAGE proteins, was shown to enhance E3 ligase activity. Actually, little is known about MAGED2 functions. Like every type II MAGE protein, it is expressed in all adult tissues. However, MAGE-D2 has the particularity to be over-expressed in numerous primary cancer and metastasis and it is now recognized as a tumour marker. This over-expression suggests that MAGED2 could be important for the process of cancerisation. MAGED2 was also shown to be a negative regulator of p53, but we did not confirm this property. Proteomic analyses also detected numerous phosphorylated or acetylated residues in response to stress and during cell cycle progression, suggesting a role in cellular signal transduction. We identified the residues targeted by ATM in MAGE-D2 and analysed the localisation of MAGED2 during the interphase and after genotoxic/nucleolar stresses. [less ▲]

Detailed reference viewed: 11 (0 ULg)
Full Text
Peer Reviewed
See detailHypervulnerability to Sound Exposure through Impaired Adaptive Proliferation of Peroxisomes.
Delmaghani, Sedigheh; Defourny, Jean; Aghaie, Asadollah et al

in Cell (2015), 163(4), 894-906

A deficiency in pejvakin, a protein of unknown function, causes a strikingly heterogeneous form of human deafness. Pejvakin-deficient (Pjvk(-/-)) mice also exhibit variable auditory phenotypes ... [more ▼]

A deficiency in pejvakin, a protein of unknown function, causes a strikingly heterogeneous form of human deafness. Pejvakin-deficient (Pjvk(-/-)) mice also exhibit variable auditory phenotypes. Correlation between their hearing thresholds and the number of pups per cage suggest a possible harmful effect of pup vocalizations. Direct sound or electrical stimulation show that the cochlear sensory hair cells and auditory pathway neurons of Pjvk(-/-) mice and patients are exceptionally vulnerable to sound. Subcellular analysis revealed that pejvakin is associated with peroxisomes and required for their oxidative-stress-induced proliferation. Pjvk(-/-) cochleas display features of marked oxidative stress and impaired antioxidant defenses, and peroxisomes in Pjvk(-/-) hair cells show structural abnormalities after the onset of hearing. Noise exposure rapidly upregulates Pjvk cochlear transcription in wild-type mice and triggers peroxisome proliferation in hair cells and primary auditory neurons. Our results reveal that the antioxidant activity of peroxisomes protects the auditory system against noise-induced damage. [less ▲]

Detailed reference viewed: 28 (4 ULg)