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287 results on '"Junier, Marie-Pierre"'

1. Challenges in glioblastoma research: focus on the tumor microenvironment

Author

Bikfalvi, Andreas, da Costa, Cristine Alves, Avril, Tony, Barnier, Jean-Vianney, Bauchet, Luc, Brisson, Lucie, Cartron, Pierre Francois, Castel, Hélène, Chevet, Eric, Chneiweiss, Hervé, Clavreul, Anne, Constantin, Bruno, Coronas, Valérie, Daubon, Thomas, Dontenwill, Monique, Ducray, Francois, Entz-Werlé, Natacha, Figarella-Branger, Dominique, Fournier, Isabelle, Frenel, Jean-Sébastien, Gabut, Mathieu, Galli, Thierry, Gavard, Julie, Huberfeld, Gilles, Hugnot, Jean-Philippe, Idbaih, Ahmed, Junier, Marie-Pierre, Mathivet, Thomas, Menei, Philippe, Meyronet, David, Mirjolet, Céline, Morin, Fabrice, Mosser, Jean, Moyal, Elisabeth Cohen-Jonathan, Rousseau, Véronique, Salzet, Michel, Sanson, Marc, Seano, Giorgio, Tabouret, Emeline, Tchoghandjian, Aurélie, Turchi, Laurent, Vallette, Francois M., Vats, Somya, Verreault, Maité, and Virolle, Thierry

Published
2023
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2. Glioblastoma cell motility depends on enhanced oxidative stress coupled with mobilization of a sulfurtransferase

Author

Saurty-Seerunghen, Mirca S., Daubon, Thomas, Bellenger, Léa, Delaunay, Virgile, Castro, Gloria, Guyon, Joris, Rezk, Ahmed, Fabrega, Sylvie, Idbaih, Ahmed, Almairac, Fabien, Burel-Vandenbos, Fanny, Turchi, Laurent, Duplus, Eric, Virolle, Thierry, Peyrin, Jean-Michel, Antoniewski, Christophe, Chneiweiss, Hervé, El-Habr, Elias A., and Junier, Marie-Pierre

Published
2022
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3. The flavonoid rutin and its aglycone quercetin modulate the microglia inflammatory profile improving antiglioma activity

Author

da Silva, Alessandra Bispo, Cerqueira Coelho, Paulo Lucas, das Neves Oliveira, Mona, Oliveira, Joana Luz, Oliveira Amparo, Jéssika Alves, da Silva, Karina Costa, Soares, Janaina Ribeiro Pereira, Pitanga, Bruno Penas Seara, dos Santos Souza, Cleide, de Faria Lopes, Giselle Pinto, da Silva, Victor Diogenes Amaral, de Fátima Dias Costa, Maria, Junier, Marie Pierre, Chneiweiss, Hervé, Moura-Neto, Vivaldo, and Costa, Silvia Lima

Published
2020
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4. CELF2 Sustains a Proliferating/OLIG2+ Glioblastoma Cell Phenotype via the Epigenetic Repression of SOX3

Author

Turchi, Laurent, primary, Sakakini, Nathalie, additional, Saviane, Gaelle, additional, Polo, Béatrice, additional, Saurty-Seerunghen, Mirca Saras, additional, Gabut, Mathieu, additional, Gouillou, Corine Auge, additional, Guerlais, Vincent, additional, Pasquier, Claude, additional, Vignais, Marie Luce, additional, Almairac, Fabien, additional, Chneiweiss, Hervé, additional, Junier, Marie-Pierre, additional, Burel-Vandenbos, Fanny, additional, and Virolle, Thierry, additional

Published
2023
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8. Introduction

Author

Junier, Marie-Pierre, Kernie, Steven G., Turksen, Kursad, Series editor, Junier, Marie-Pierre, editor, and Kernie, Steven G., editor

Published
2014
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10. The oncolytic virus Delta-24-RGD elicits an antitumor effect in pediatric glioma and DIPG mouse models

Author

Martínez-Vélez, Naiara, Garcia-Moure, Marc, Marigil, Miguel, González-Huarriz, Marisol, Puigdelloses, Montse, Gallego Pérez-Larraya, Jaime, Zalacaín, Marta, Marrodán, Lucía, Varela-Guruceaga, Maider, Laspidea, Virginia, Aristu, Jose Javier, Ramos, Luis Isaac, Tejada-Solís, Sonia, Díez-Valle, Ricardo, Jones, Chris, Mackay, Alan, Martínez-Climent, Jose A., García-Barchino, Maria Jose, Raabe, Eric, Monje, Michelle, Becher, Oren J., Junier, Marie Pierre, El-Habr, Elias A., Chneiweiss, Herve, Aldave, Guillermo, Jiang, Hong, Fueyo, Juan, Patiño-García, Ana, Gomez-Manzano, Candelaria, and Alonso, Marta M.

Published
2019
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11. Data from ERK-Mediated Loss of miR-199a-3p and Induction of EGR1 Act as a “Toggle Switch” of GBM Cell Dedifferentiation into NANOG- and OCT4-Positive Cells

Author

Almairac, Fabien, primary, Turchi, Laurent, primary, Sakakini, Nathalie, primary, Debruyne, David Nicolas, primary, Elkeurti, Sarah, primary, Gjernes, Elisabet, primary, Polo, Beatrice, primary, Bianchini, Laurence, primary, Fontaine, Denys, primary, Paquis, Philippe, primary, Chneiweiss, Herve, primary, Junier, Marie-Pierre, primary, Verrando, Patrick, primary, Burel-Vandenbos, Fanny, primary, and Virolle, Thierry, primary

Published
2023
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12. Supplementary Data from ERK-Mediated Loss of miR-199a-3p and Induction of EGR1 Act as a “Toggle Switch” of GBM Cell Dedifferentiation into NANOG- and OCT4-Positive Cells

Author

Almairac, Fabien, primary, Turchi, Laurent, primary, Sakakini, Nathalie, primary, Debruyne, David Nicolas, primary, Elkeurti, Sarah, primary, Gjernes, Elisabet, primary, Polo, Beatrice, primary, Bianchini, Laurence, primary, Fontaine, Denys, primary, Paquis, Philippe, primary, Chneiweiss, Herve, primary, Junier, Marie-Pierre, primary, Verrando, Patrick, primary, Burel-Vandenbos, Fanny, primary, and Virolle, Thierry, primary

Published
2023
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13. Supplementary tables S1-S3 from ERK-Mediated Loss of miR-199a-3p and Induction of EGR1 Act as a “Toggle Switch” of GBM Cell Dedifferentiation into NANOG- and OCT4-Positive Cells

Author

Almairac, Fabien, primary, Turchi, Laurent, primary, Sakakini, Nathalie, primary, Debruyne, David Nicolas, primary, Elkeurti, Sarah, primary, Gjernes, Elisabet, primary, Polo, Beatrice, primary, Bianchini, Laurence, primary, Fontaine, Denys, primary, Paquis, Philippe, primary, Chneiweiss, Herve, primary, Junier, Marie-Pierre, primary, Verrando, Patrick, primary, Burel-Vandenbos, Fanny, primary, and Virolle, Thierry, primary

Published
2023
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14. figure legends and tables from ERK-Mediated Loss of miR-199a-3p and Induction of EGR1 Act as a “Toggle Switch” of GBM Cell Dedifferentiation into NANOG- and OCT4-Positive Cells

Author

Almairac, Fabien, primary, Turchi, Laurent, primary, Sakakini, Nathalie, primary, Debruyne, David Nicolas, primary, Elkeurti, Sarah, primary, Gjernes, Elisabet, primary, Polo, Beatrice, primary, Bianchini, Laurence, primary, Fontaine, Denys, primary, Paquis, Philippe, primary, Chneiweiss, Herve, primary, Junier, Marie-Pierre, primary, Verrando, Patrick, primary, Burel-Vandenbos, Fanny, primary, and Virolle, Thierry, primary

Published
2023
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16. Changes in chromatin state reveal ARNT2 at a node of a tumorigenic transcription factor signature driving glioblastoma cell aggressiveness

Author

Bogeas, Alexandra, Morvan-Dubois, Ghislaine, El-Habr, Elias A., Lejeune, François-Xavier, Defrance, Matthieu, Narayanan, Ashwin, Kuranda, Klaudia, Burel-Vandenbos, Fanny, Sayd, Salwa, Delaunay, Virgile, Dubois, Luiz G., Parrinello, Hugues, Rialle, Stéphanie, Fabrega, Sylvie, Idbaih, Ahmed, Haiech, Jacques, Bièche, Ivan, Virolle, Thierry, Goodhardt, Michele, Chneiweiss, Hervé, and Junier, Marie-Pierre

Published
2017
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17. A driver role for GABA metabolism in controlling stem and proliferative cell state through GHB production in glioma

Author

El-Habr, Elias A., Dubois, Luiz G., Burel-Vandenbos, Fanny, Bogeas, Alexandra, Lipecka, Joanna, Turchi, Laurent, Lejeune, François-Xavier, Coehlo, Paulo Lucas Cerqueira, Yamaki, Tomohiro, Wittmann, Bryan M., Fareh, Mohamed, Mahfoudhi, Emna, Janin, Maxime, Narayanan, Ashwin, Morvan-Dubois, Ghislaine, Schmitt, Charlotte, Verreault, Maité, Oliver, Lisa, Sharif, Ariane, Pallud, Johan, Devaux, Bertrand, Puget, Stéphanie, Korkolopoulou, Penelope, Varlet, Pascale, Ottolenghi, Chris, Plo, Isabelle, Moura-Neto, Vivaldo, Virolle, Thierry, Chneiweiss, Hervé, and Junier, Marie-Pierre

Published
2017
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18. The anti‐hypertensive drug prazosin inhibits glioblastoma growth via the PKCδ‐dependent inhibition of the AKT pathway

Author

Assad Kahn, Suzana, Costa, Silvia Lima, Gholamin, Sharareh, Nitta, Ryan T, Dubois, Luiz Gustavo, Fève, Marie, Zeniou, Maria, Coelho, Paulo Lucas Cerqueira, El‐Habr, Elias, Cadusseau, Josette, Varlet, Pascale, Mitra, Siddhartha S, Devaux, Bertrand, Kilhoffer, Marie‐Claude, Cheshier, Samuel H, Moura‐Neto, Vivaldo, Haiech, Jacques, Junier, Marie‐Pierre, and Chneiweiss, Hervé

Published
2016
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19. Human glioblastoma cell motility depends on the activity of the cysteine metabolism enzyme 3‐Mercaptopyruvate sulfurtransferase

Author

Saurty-Seerunghen, Mirca S, primary, Daubon, Thomas, additional, Bellenger, Lea, additional, Delaunay, Virgile, additional, Castro, Gloria, additional, Guyon, Joris, additional, Rezk, Ahmed, additional, Fabrega, Sylvie, additional, Idbaih, Ahmed, additional, Almairac, Fabien, additional, Burel-Vandenbos, Fanny, additional, Turchi, Laurent, additional, Virolle, Thierry, additional, Peyrin, Jean-Michel, additional, Antoniewski, Christophe, additional, Chneiweiss, Herve, additional, El-Habr, Elias A, additional, and Junier, Marie-Pierre, additional

Published
2022
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21. The anti-hypertensive drug prazosin inhibits glioblastoma growth via the PKCδ-dependent inhibition of the AKT pathway

Author

Kahn, Suzana Assad, Costa, Silvia Lima, Gholamin, Sharareh, Nitta, Ryan T, Dubois, Luiz Gustavo, Fève, Marie, Zeniou, Maria, Coelho, Paulo Lucas Cerqueira, El-Habr, Elias, Cadusseau, Josette, Varlet, Pascale, Mitra, Siddhartha S, Devaux, Bertrand, Kilhoffer, Marie-Claude, Cheshier, Samuel H, Moura-Neto, Vivaldo, Haiech, Jacques, Junier, Marie-Pierre, and Chneiweiss, Hervé

Published
2016
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22. PAF and Hypothalamic Secretions in the Rat

Author

Dray, Fernand, Rougeot, Catherine, Tiberghien, Christopher, Junier, Marie-Pierre, Massarelli, Raphaël, editor, Horrocks, Lloyd A., editor, Kanfer, Julian N., editor, and Löffelholz, Konrad, editor

Published
1993
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29. ERK-Mediated Loss of miR-199a-3p and Induction of EGR1 Act as a “Toggle Switch” of GBM Cell Dedifferentiation into NANOG- and OCT4-Positive Cells

Author

Almairac, Fabien, primary, Turchi, Laurent, additional, Sakakini, Nathalie, additional, Debruyne, David Nicolas, additional, Elkeurti, Sarah, additional, Gjernes, Elisabet, additional, Polo, Beatrice, additional, Bianchini, Laurence, additional, Fontaine, Denys, additional, Paquis, Philippe, additional, Chneiweiss, Herve, additional, Junier, Marie-Pierre, additional, Verrando, Patrick, additional, Burel-Vandenbos, Fanny, additional, and Virolle, Thierry, additional

Published
2020
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33. MOESM3 of Capture at the single cell level of metabolic modules distinguishing aggressive and indolent glioblastoma cells

Author

Saurty-Seerunghen, Mirca, LĂŠa Bellenger, El-Habr, Elias, Delaunay, Virgile, Garnier, Delphine, HervĂŠ Chneiweiss, Antoniewski, Christophe, Morvan-Dubois, Ghislaine, and Junier, Marie-Pierre

Abstract

Additional file 3: Figure S1. Removing cells with low-complexity transcriptomes and unsupervised grouping analysis of GBM and normal cells simultaneously. Figure S2. Maintenance of tumor-driven cell grouping regardless of the mode of data normalization or filtering. Figure S3. Numbers of transcripts and genes per TumHIGH versus TumLOW cell. Figure S4. Signature-based analytical workflow. Figure S5. Main metabolic pathways containing the metabolic enzyme genes overexpressed in TumHIGH GBM cells and tissues. Figure S6. Similar metabolic modules distinguish TumHIGH and TumLOW GBM cells independently from EGFR amplification. Figure S7. Increased ELOVL2 expression is associated with increased tumor burden. Figure S8. Knocking down ELOVL2 expression using a second sh ELOVL2 construct. Figure S9. GBM cell tumorigenic state and extracellular vesicle production and release.

Published
2019
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35. Protein interaction mapping: A Drosophila case study

Author

Formstecher, Etienne, Mukherjee, Ashim, Johannes, Ludger, Goud, Bruno, Papadopoulo, Dora, Junier, Marie-Pierre, Mirouse, Vincent, Perez, Franck, Gunzburg, Jean de, Aresta, Sandra, Hamburger, Alexandre, Collura, Vincent, Meil, Alain, Terhin, Alexandra, Plessis, Anne, Reverdy, Celine, Brun, Christine, Betin,Virginie, Jacq, Bernard, Maire, Sophie, Arpin, Monique, Rosse, Carine, Bellaiche, Yohanns, Bellusci, Saverio, Benaroch, Phillippe, Bornens, Michel, Saule, Simon, Chanet, Roland, Vincent, Alia, Girault, Jean-Antoine, Stoppa-Lyonnet, Dominique, White, Micheal, Doye, Valerie, Chavrier, Philippe, Delattre, Olivier, Legrain, Pierre, Fehon, Richard, Faye, Gerard, and Galli, Thierry

Subjects
Chromosome mapping -- Research, Oncogenes -- Research, DNA -- Research, Drosophila -- Genetic aspects, Genetic research, Health
Abstract

A high througput yeast two-hybrid (Y2H)-based technology is used to screen 102 bait proteins from Drosophila melanogaster, most of them orthologous to human cancer-related and/or signaling proteins, against high-complexity fly cDNA libraries. Analysis of the differences in data sets and methods suggests alternative strategies to enhance the accuracy and comprehensiveness of the post-genomic generation of broad-scale protein interaction maps.

Published
2005

38. WNK1 kinase and its partners Akt, SGK1 and NBC-family Na+/HCO3– cotransporters are potential therapeutic targets for glioblastoma stem-like cells linked to Bisacodyl signaling

Author

Chen, Wanyin, Zebaze, Leonel Nguekeu, Dong, Jihu, Chezeau, Laëtitia, Inquimbert, Perrine, Hugel, Sylvain, Niu, Songlin, Bihel, Frédéric, Boutant, Emmanuel, Real, Eleonore, Villa, Pascal, Junier, Marie-Pierre, Chneiweiss, Herve, Hibert, Marcel, Haiech, Jacques, Kilhoffer, Marie-Claude, Zeniou, Maria, Laboratoire d'Innovation Thérapeutique (LIT), Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut de Chimie du CNRS (INC), Institut des Neurosciences Cellulaires et Intégratives (INCI), Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS), Institut de Science des Matériaux de Mulhouse (IS2M), Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Biophotonique et Pharmacologie - UMR 7213 (LBP), Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA)), Neurobiologie & Développement (N&D), Centre National de la Recherche Scientifique (CNRS), Biomolécules et innovation thérapeutique (IGLBIT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de psychiatrie et neurosciences (U894 / UMS 1266), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Plasticité gliale et neuro-oncologie = Glial Plasticity (NPS-04), Neurosciences Paris Seine (NPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Institut Gilbert-Laustriat : Biomolécules, Biotechnologie, Innovation Thérapeutique, HUGEL, Sylvain, Université de Strasbourg (UNISTRA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS), Neuroscience Paris Seine (NPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
[SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2018
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39. Changes in chromatin state reveal ARNT2 at a node of a tumorigenic transcription factor signature driving glioblastoma cell aggressiveness

Author

Bogeas, Alexandra, Morvan-Dubois, Ghislaine, El-Habr, Elias A., Lejeune, François-Xavier, Defrance, Matthieu, Narayanan, Ashwin, Kuranda, Klaudia, Burel-Vandenbos, Fanny, Sayd, Salwa, Delaunay, Virgile, Dubois, Luiz G., Parrinello, Hugues, Rialle, Stéphanie, Fabrega, Sylvie, Idbaih, Ahmed, Haiech, Jacques, Bièche, Ivan, Virolle, Thierry, Goodhardt, Michele, Chneiweiss, Hervé, Junier, Marie-Pierre, Neurosciences Paris Seine (NPS), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Adaptation Biologique et Vieillissement = Biological Adaptation and Ageing (B2A), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Interuniversity Institute of Bioinformatics in Brussels (IB2), Université libre de Bruxelles (ULB)-Vrije Universiteit Brussel (VUB), Différenciation et progression tumorale des lymphocytes, École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Biologie Valrose (IBV), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Central d’Anatomie Pathologique [Hôpital Pasteur, Nice] (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Hôpital Pasteur [Nice] (CHU), Institut de Génomique Fonctionnelle - Montpellier GenomiX (IGF MGX), Institut de Génomique Fonctionnelle (IGF), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), BioCampus Montpellier (BCM), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Plateforme Vecteurs Viraux et Transfert de Gènes [SFR Necker] (VVTG), Structure Fédérative de Recherche Necker (SFR Necker - UMS 3633 / US24), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Innovation Thérapeutique (LIT), Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut de Chimie du CNRS (INC), Département de Génétique [Institut Curie, Paris] (Unité de Pharmacogénomique), Institut Curie [Paris], This work was supported by La Ligue nationale contre le cancer (Equipe Labellisée LIGUE 2013, Equipe Labelisée LIGUE 2016 HC/MPJ), Institut National du Cancer (INCa 2012-1-PLBIO-07-INSERM-1, INCa-AAP Epigénétique et cancer 2014, HC/MPJ), Fondation pour la recherche sur le cerveau (FRC), Agence Nationale de la Recherche (ANR-13-1SV1-0004-03, JH/HC), Cancéropole Région Ile-de-France (EAE and AB fellowships), CAPES/COFECUB (Coordination pour le perfectionnement du personnel de l’enseignement supérieur/Comité français d’evaluation de la coopération universitaire et scientifique avec le Brésil, LGD fellowship), and Fundação Ary Frauzino para o Câncer (LGD fellowship)., Neuroscience Paris Seine (NPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Interuniversity Institute of Bioinformatics in Brussels [ULB], Université Libre de Bruxelles [Bruxelles] (ULB), École pratique des hautes études (EPHE)-Institut Universitaire d'Hématologie (IUH), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Hôpital Pasteur [Nice] (CHU), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Institut Curie, Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-BioCampus (BCM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), BioCampus (BCM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg (UNISTRA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), and Goodhardt, Michele

Subjects
ChIP, Mice, Nude, Brain cancer, Epigenesis, Genetic, [SCCO]Cognitive science, Neurologie, Basic Helix-Loop-Helix Transcription Factors, Médecine légale, Animals, Humans, Neoplasm Invasiveness, Cells, Cultured, Aged, Homeodomain Proteins, Original Paper, Brain Neoplasms, Xenograft, Aryl Hydrocarbon Receptor Nuclear Translocator, SOX9 Transcription Factor, [SCCO] Cognitive science, Glioma, Middle Aged, Oligodendrocyte Transcription Factor 2, Chromatin, Gene Expression Regulation, Neoplastic, Histone Code, Pathologie générale, Gene Knockdown Techniques, POU Domain Factors, Neoplastic Stem Cells, Glioblastoma, Sciences cognitives, Neoplasm Transplantation
Abstract

Although a growing body of evidence indicates that phenotypic plasticity exhibited by glioblastoma cells plays a central role in tumor development and post-therapy recurrence, the master drivers of their aggressiveness remain elusive. Here we mapped the changes in active (H3K4me3) and repressive (H3K27me3) histone modifications accompanying the repression of glioblastoma stem-like cells tumorigenicity. Genes with changing histone marks delineated a network of transcription factors related to cancerous behavior, stem state, and neural development, highlighting a previously unsuspected association between repression of ARNT2 and loss of cell tumorigenicity. Immunohistochemistry confirmed ARNT2 expression in cell sub-populations within proliferative zones of patients’ glioblastoma. Decreased ARNT2 expression was consistently observed in non-tumorigenic glioblastoma cells, compared to tumorigenic cells. Moreover, ARNT2 expression correlated with a tumorigenic molecular signature at both the tissue level within the tumor core and at the single cell level in the patients’ tumors. We found that ARNT2 knockdown decreased the expression of SOX9, POU3F2 and OLIG2, transcription factors implicated in glioblastoma cell tumorigenicity, and repressed glioblastoma stem-like cell tumorigenic properties in vivo. Our results reveal ARNT2 as a pivotal component of the glioblastoma cell tumorigenic signature, located at a node of a transcription factor network controlling glioblastoma cell aggressiveness., SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2018
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42. CD133, CD15/SSEA-1, CD34 or side populations do not resume tumor-initiating properties of long-term cultured cancer stem cells from human malignant glio-neuronal tumors

Author

Mihalescu-Maingot Maria, Berhneim Alain, Leonard Nadine, Thirant Cécile, Renault-Mihara François, Cadusseau Josette, Raponi Eric, Coulombel Laure, Varlet Pascale, Romao Luciana, Patru Cristina, Haiech Jacques, Bièche Ivan, Moura-Neto Vivaldo, Daumas-Duport Catherine, Junier Marie-Pierre, and Chneiweiss Hervé

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background Tumor initiating cells (TICs) provide a new paradigm for developing original therapeutic strategies. Methods We screened for TICs in 47 human adult brain malignant tumors. Cells forming floating spheres in culture, and endowed with all of the features expected from tumor cells with stem-like properties were obtained from glioblastomas, medulloblastoma but not oligodendrogliomas. Results A long-term self-renewal capacity was particularly observed for cells of malignant glio-neuronal tumors (MGNTs). Cell sorting, karyotyping and proteomic analysis demonstrated cell stability throughout prolonged passages. Xenografts of fewer than 500 cells in Nude mouse brains induced a progressively growing tumor. CD133, CD15/LeX/Ssea-1, CD34 expressions, or exclusion of Hoechst dye occurred in subsets of cells forming spheres, but was not predictive of their capacity to form secondary spheres or tumors, or to resist high doses of temozolomide. Conclusions Our results further highlight the specificity of a subset of high-grade gliomas, MGNT. TICs derived from these tumors represent a new tool to screen for innovative therapies.

Published
2010
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46. A driver role for GABA metabolism in controlling stem and proliferative cell state through GHB production in glioma

Author

El-Habr, Elias A. (author), Dubois, Luiz G. (author), Burel-Vandenbos, Fanny (author), Bogeas, Alexandra (author), Lipecka, Joanna (author), Turchi, Laurent (author), Lejeune, François Xavier (author), Coehlo, Paulo Lucas Cerqueira (author), Yamaki, Tomohiro (author), Wittmann, Bryan M. (author), Fareh, M. (author), Mahfoudhi, Emna (author), Janin, Maxime (author), Narayanan, Ashwin (author), Morvan-Dubois, Ghislaine (author), Schmitt, Charlotte (author), Verreault, Maité (author), Oliver, Lisa (author), Sharif, Ariane (author), Pallud, Johan (author), Devaux, Bertrand (author), Puget, Stéphanie (author), Korkolopoulou, Penelope (author), Varlet, Pascale (author), Ottolenghi, Chris (author), Plo, Isabelle (author), Moura-Neto, Vivaldo (author), Virolle, Thierry (author), Chneiweiss, Hervé (author), Junier, Marie Pierre (author), El-Habr, Elias A. (author), Dubois, Luiz G. (author), Burel-Vandenbos, Fanny (author), Bogeas, Alexandra (author), Lipecka, Joanna (author), Turchi, Laurent (author), Lejeune, François Xavier (author), Coehlo, Paulo Lucas Cerqueira (author), Yamaki, Tomohiro (author), Wittmann, Bryan M. (author), Fareh, M. (author), Mahfoudhi, Emna (author), Janin, Maxime (author), Narayanan, Ashwin (author), Morvan-Dubois, Ghislaine (author), Schmitt, Charlotte (author), Verreault, Maité (author), Oliver, Lisa (author), Sharif, Ariane (author), Pallud, Johan (author), Devaux, Bertrand (author), Puget, Stéphanie (author), Korkolopoulou, Penelope (author), Varlet, Pascale (author), Ottolenghi, Chris (author), Plo, Isabelle (author), Moura-Neto, Vivaldo (author), Virolle, Thierry (author), Chneiweiss, Hervé (author), and Junier, Marie Pierre (author)

Abstract

Cell populations with differing proliferative, stem-like and tumorigenic states co-exist in most tumors and especially malignant gliomas. Whether metabolic variations can drive this heterogeneity by controlling dynamic changes in cell states is unknown. Metabolite profiling of human adult glioblastoma stem-like cells upon loss of their tumorigenicity revealed a switch in the catabolism of the GABA neurotransmitter toward enhanced production and secretion of its by-product GHB (4-hydroxybutyrate). This switch was driven by succinic semialdehyde dehydrogenase (SSADH) downregulation. Enhancing GHB levels via SSADH downregulation or GHB supplementation triggered cell conversion into a less aggressive phenotypic state. GHB affected adult glioblastoma cells with varying molecular profiles, along with cells from pediatric pontine gliomas. In all cell types, GHB acted by inhibiting α-ketoglutarate-dependent Ten–eleven Translocations (TET) activity, resulting in decreased levels of the 5-hydroxymethylcytosine epigenetic mark. In patients, low SSADH expression was correlated with high GHB/α-ketoglutarate ratios, and distinguished weakly proliferative/differentiated glioblastoma territories from proliferative/non-differentiated territories. Our findings support an active participation of metabolic variations in the genesis of tumor heterogeneity., BN/Chirlmin Joo Lab

Published
2017
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47. Cell-based therapy using miR-302-367 expressing cells represses glioblastoma growth

Author

Fareh, M. (author), Almairac, Fabien (author), Turchi, Laurent (author), Burel-Vandenbos, Fanny (author), Paquis, Philippe (author), Fontaine, Denys (author), Lacas-Gervais, Sandra (author), Junier, Marie Pierre (author), Chneiweiss, Hervé (author), Virolle, Thierry (author), Fareh, M. (author), Almairac, Fabien (author), Turchi, Laurent (author), Burel-Vandenbos, Fanny (author), Paquis, Philippe (author), Fontaine, Denys (author), Lacas-Gervais, Sandra (author), Junier, Marie Pierre (author), Chneiweiss, Hervé (author), and Virolle, Thierry (author)

Abstract

Glioblastomas are incurable primary brain tumors that affect patients of all ages. The aggressiveness of this cancer has been attributed in part to the persistence of treatment-resistant glioblastoma stem-like cells. We have previously discovered the tumor-suppressor properties of the microRNA cluster miR-302-367, representing a potential treatment for glioblastoma. Here, we attempted to develop a cell-based therapy by taking advantage of the capability of glioma cells to secrete exosomes that enclose small RNA molecules. We engineered primary glioma cells to stably express the miR-302-367. Remarkably, these cells altered, in a paracrine-dependent manner, the expression of stemness markers, the proliferation and the tumorigenicity of neighboring glioblastoma cells. Further characterization of the secretome derived from miR-302-367 expressing cells showed that a large amount of miR-302-367 was enclosed in exosomes, which were internalized by the neighboring glioblastoma cells. This miR-302-367 cell-To-cell transfer resulted in the inhibition of its targets such as CXCR4/SDF1, SHH, cyclin D, cyclin A and E2F1. Orthotopic xenograft of miR-302-367-expressing cells together with glioblastoma stem-like cells efficiently altered the tumor development in mice brain., BN/Chirlmin Joo Lab

Published
2017
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48. A driver role for GABA metabolism in controlling stem and proliferative cell state through GHB production in glioma

Author

El-Habr, Elias A., Dubois, Luiz G., Burel-Vandenbos, Fanny, Bogeas, Alexandra, Lipecka, Joanna, Turchi, Laurent, Lejeune, François-Xavier, Coehlo, Paulo Lucas Cerqueira, Yamaki, Tomohiro, Wittmann, Bryan M., Fareh, Mohamed, Mahfoudhi, Emna, Janin, Maxime, Narayanan, Ashwin, Morvan-Dubois, Ghislaine, Schmitt, Charlotte, Verreault, Maité, Oliver, Lisa, Sharif, Ariane, Pallud, Johan, Devaux, Bertrand, Puget, Stéphanie, Korkolopoulou, Penelope, Varlet, Pascale, Ottolenghi, Chris, Plo, Isabelle, Moura-Neto, Vivaldo, Virolle, Thierry, Chneiweiss, Hervé, Junier, Marie-Pierre, Neurosciences Paris Seine (NPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Instituto Estadual do cerebro Paulo Niemeyer, Institut de Biologie Valrose (IBV), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Service de pathologie, Centre Hospitalier Universitaire de Nice (CHU Nice), Institut de psychiatrie et neurosciences (U894 / UMS 1266), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Adaptation Biologique et Vieillissement = Biological Adaptation and Ageing (B2A), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Metabolon, Hématopoïèse normale et pathologique, Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de biochimie métabolique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 (JPArc), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille, Université Paris Descartes - Paris 5 (UPD5), Department of Paediatric Neurosurgery, Necker Enfants Malades Hospital, Paris, France., Department of Haematopathology, National and Kapodistrian University of Athens, Laikon General Hospital, Service de neuropathologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Sainte-Anne, Hématopoïèse normale et pathologique (U1170 Inserm), This work was supported by La Ligue nationale contre le cancer (Equipe Labellisée LIGUE 2013, Equipe Labelisée LIGUE 2016 HC/MPJ), Institut National du Cancer (INCa 2012-1-PLBIO-07-INSERM-1, HC/MPJ), Cancéropole Région Ile-de-France (EAE and AB fellowships), CAPES/COFECUB (Coordination pour le perfectionnement du personnel de l’enseignement supérieur/Comité français d’evaluation de la coopération universitaire et scientifique avec le Brésil, VMN and LGD fellowship), Fundação Ary Frauzino para o Câncer (LGD fellowship), and Neurosurgeon college of Chiba prefecture, Japan (TY fellowship)., Neuroscience Paris Seine ( NPS ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Institut de Biologie Valrose ( IBV ), Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Nice Sophia Antipolis ( UNS ), Université Côte d'Azur ( UCA ) -Université Côte d'Azur ( UCA ), CHU Nice, Centre de Psychiatrie et Neurosciences ( CPN - U894 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Adaptation Biologique et Vieillissement = Biological Adaptation and Ageing ( B2A ), Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut Gustave Roussy ( IGR ) -Université Paris-Sud - Paris 11 ( UP11 ), CHU Necker - Enfants Malades [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute ( ICM ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -CHU Pitié-Salpêtrière [APHP]-Centre National de la Recherche Scientifique ( CNRS ), Centre de Recherche en Cancérologie / Nantes - Angers ( CRCNA ), CHU Angers-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Hôpital Laennec-Centre National de la Recherche Scientifique ( CNRS ) -Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes ( CHU Nantes ), Centre de recherche Jean-Pierre Aubert-Neurosciences et Cancer, Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Lille, Droit et Santé, Université Paris Descartes - Paris 5 ( UPD5 ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Sainte-Anne, Hématopoïèse normale et pathologique ( U1170 Inserm ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut Gustave Roussy ( IGR ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Neuroscience Paris Seine (NPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Gustave Roussy (IGR)-Université Paris-Sud - Paris 11 (UP11), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [APHP], Centre de Recherche en Cancérologie / Nantes - Angers (CRCNA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Sainte-Anne, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Nice Sophia Antipolis (1965 - 2019) (UNS), Centre de Psychiatrie et Neurosciences (U894), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, National and Kapodistrian University of Athens (NKUA), and Bernardo, Elizabeth

Subjects
Male, Carcinogenesis, Clinical Neurology, Hydroxybutyrates, Mice, Nude, [SDV.CAN]Life Sciences [q-bio]/Cancer, Brain cancer, Pathology and Forensic Medicine, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, Cellular and Molecular Neuroscience, GABA, [SDV.CAN] Life Sciences [q-bio]/Cancer, Animals, Humans, ALDH5A1, Child, gamma-Aminobutyric Acid, Aged, Cell Proliferation, Original Paper, Valproate, Cell Death, Brain Neoplasms, Cancer stem cell, Brain, Glioma, Middle Aged, 5-hmC, Child, Preschool, Neoplastic Stem Cells, DIPG, Female, Succinate-Semialdehyde Dehydrogenase, Neoplasm Transplantation
Abstract

Cell populations with differing proliferative, stem-like and tumorigenic states co-exist in most tumors and especially malignant gliomas. Whether metabolic variations can drive this heterogeneity by controlling dynamic changes in cell states is unknown. Metabolite profiling of human adult glioblastoma stem-like cells upon loss of their tumorigenicity revealed a switch in the catabolism of the GABA neurotransmitter toward enhanced production and secretion of its by-product GHB (4-hydroxybutyrate). This switch was driven by succinic semialdehyde dehydrogenase (SSADH) downregulation. Enhancing GHB levels via SSADH downregulation or GHB supplementation triggered cell conversion into a less aggressive phenotypic state. GHB affected adult glioblastoma cells with varying molecular profiles, along with cells from pediatric pontine gliomas. In all cell types, GHB acted by inhibiting α-ketoglutarate-dependent Ten–eleven Translocations (TET) activity, resulting in decreased levels of the 5-hydroxymethylcytosine epigenetic mark. In patients, low SSADH expression was correlated with high GHB/α-ketoglutarate ratios, and distinguished weakly proliferative/differentiated glioblastoma territories from proliferative/non-differentiated territories. Our findings support an active participation of metabolic variations in the genesis of tumor heterogeneity. Electronic supplementary material The online version of this article (doi:10.1007/s00401-016-1659-5) contains supplementary material, which is available to authorized users.

Published
2016
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50. Bisacodyl and its cytotoxic activity on human glioblastoma stem-like cells. Implication of inositol 1,4,5-triphosphate receptor dependent calcium signaling

Author

Dong, Jihu, primary, Aulestia, Francisco J., additional, Assad Kahn, Suzana, additional, Zeniou, Maria, additional, Dubois, Luiz Gustavo, additional, El-Habr, Elias A., additional, Daubeuf, François, additional, Tounsi, Nassera, additional, Cheshier, Samuel H., additional, Frossard, Nelly, additional, Junier, Marie-Pierre, additional, Chneiweiss, Hervé, additional, Néant, Isabelle, additional, Moreau, Marc, additional, Leclerc, Catherine, additional, Haiech, Jacques, additional, and Kilhoffer, Marie-Claude, additional

Published
2017
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