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DTSTART;TZID=Europe/Paris:20231013T114000
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DTSTAMP:20260409T222556
CREATED:20230928T124956Z
LAST-MODIFIED:20231012T141750Z
UID:57506-1697197200-1697199000@www.crct-inserm.fr
SUMMARY:Conférence : BMP2 and BMP7 cooperate with H3.3K27M to promote quiescence and invasiveness in pediatric diffuse midline gliomas | Marie Castets\, CRCL
DESCRIPTION:Important : reportée de 11h40 à 12h10 \nPour suivre la conférence à distance\, cliquez ici. \nAbstract : \nPediatric diffuse midline gliomas (pDMG) are an aggressive type of childhood cancer with a fatal outcome. Their major epigenetic determinism has become clear\, notably with the identification of K27M mutations in histone H3. However\, the synergistic oncogenic mechanisms that induce and maintain tumor cell phenotype have yet to be deciphered.\nIn 20 to 30% of cases\, these tumors have an altered BMP signaling pathway with an oncogenic mutation on the BMP type I receptor ALK2\, encoded by ACVR1. However\, the potential impact of the BMP pathway in tumors non-mutated for ACVR1 is less clear. By integrating bulk\, single-cell and spatial transcriptomic data\, we show here that the BMP signaling pathway is activated at similar levels between ACVR1 wild type and mutant tumors and identify BMP2 and BMP7 as putative activators of the pathway in a specific subpopulation of cells. By using both pediatric isogenic glioma lines genetically modified to overexpress H3.3K27M and patients-derived DIPG cell lines\, we demonstrate that BMP2/7 synergizes with H3.3K27M to induce a transcriptomic rewiring associated with a quiescent but invasive cell state. These data suggest a generic oncogenic role for the BMP pathway in gliomagenesis of pDMG and pave the way for specific targeting of downstream effectors mediating the BMP/K27M crosstalk. \n  \nPublication shortlist : \nModeling the next-generation of fusion-negative rhabdomyosarcoma 3D-organoids to predict effective drug combinations: a proof-of-concept on cell death inducers. Clara Savary\, Paul Huchedé\, Léa Luciana\, Arthur Tourbez\, Clémence Deligne\, Cécile Picard\, Thomas Diot\, Claire Coquet\, Nina Meynard\, Marion Le Grand\, Laurie Tonon\, Nicolas Gadot\, Cyril Degletagne\, Sophie Léon\, Valéry Attignon\, Alexandra Bomane\, Isabelle Rochet\, Kevin Müller\, Virginie Mournetas\, Christophe Bergeron\, Paul Rinaudo\, Aurélie Dutour\, Martine Cordier-Bussat\, Frédérique Dijoud\, Nadège Corradini\, View ORCID ProfileDelphine Maucort-Boulch\, Eddy Pasquier\, View ORCID ProfileJean-Yves Blay\, Marie Castets*\, Laura Broutier*. In revision\, Cell Reports Medicine. Available on Biorxiv.\nBMP2 and BMP7 cooperate with H3.3K27M to promote quiescence and invasiveness in pediatric diffuse midline gliomas. Paul Huchedé\, Swann Meyer\, Clément Berthelot\, Maud Hamadou\, Adrien Bertrand-Chapel\, Andria Rakotomalala\, Line Manceau\, Julia Tomine\, Nicolas Lespinasse\, Paul Lewandowski\, Martine Cordier-Bussat\, Laura Broutier\, Aurélie Dutour\, Isabelle Rochet\, Jean-Yves Blay\, Cyril Degletagne\, Valéry Attignon\, Angel Montero-Carcaboso\, Marion Le Grand\, Eddy Pasquier\, Alexandre Vasiljevic\, Pascale Gilardi-Hebenstreit\, Samuel Meignan\, Pierre Leblond\, Vanessa Ribes\, Erika Cosset\, Marie Castets. eLife\, in press. Available on Biorxiv.\nThe TLR3 L412F polymorphism prevents TLR3-mediated tumor cell death induction in pediatric sarcomas. Bisaccia J\, Meyer S\, Bertrand-Chapel A\, Hecquet Q\, Barbet V\, Kaniewski B\, Léon S\, Gadot N\, Rochet I\, Fajnorova I\, Leblond P\, Cordier-Bussat M\, Corradini N\, Vasiljevic A\, Billaud M\, Picard C\, Broutier L\, Gallerne C\, Dutour A\, Blay JY\, Castets M. Cell Death Discov. 2023 Jul 7;9(1):230. doi: 10.1038/s41420-023-01513-y. PMID: 37414800\nHolistic pediatric oncology: towards a second Copernican revolution. André N\, Castets M\, Pasquier E\, Mehlen P. Trends Cancer. 2023 Sep;9(9):693-696.\nThe Intricate Epigenetic and Transcriptional Alterations in Pediatric High-Grade Gliomas: Targeting the Crosstalk as the Oncogenic Achilles’ Heel. Huchedé P\, Leblond P\, Castets M. Biomedicines. 2022 Jun 3;10(6):1311. doi: 10.3390/biomedicines10061311. PMID: 35740334\nThe Ectodysplasin receptor EDAR acts as a tumor suppressor in melanoma by conditionally inducing cell death. Vial J\, Royet A\, Cassier P\, Tortereau A\, Dinvaut S\, Maillet D\, Gratadou-Hupon L\, Creveaux M\, Sadier A\, Tondeur G\, Léon S\, Depaepe L\, Pantalacci S\, de la Fouchardière A\, Micheau O\, Dalle S\, Laudet V\, Mehlen P\, Castets M. Cell Death Differ. 2019 Mar;26(3):443-454. doi: 10.1038/s41418-018-0128-1. Epub 2018 May 31. PMID: 29855541 \nMini Bio \nMarie Castets\, PhD\nChef de l’équipe « Mort cellulaire et cancers pédiatriques » au Centre de Recherche en cancérologie de Lyon\, CRCL\, Centre Léon Bérard\, Lyon\, elle est aussi à l’origine du réseau national React4Kids lancé en 2018\, et qui réunit actuellement l’ensemble des scientifiques français développant des axes de recherche fondamentale et translationnelle en cancérologie pédiatrique.\n« Face à la complexité du cancer\, il n’y a qu’en mutualisant nos expertises et nos outils que nous parviendrons à améliorer de manière significative la prise en charge des patients. Et si cette collaboration doit évidemment se faire au niveau international\, il convient de s’appuyer sur une forte structuration nationale pour avancer de manière efficace dans la compréhension des mécanismes moléculaires impliqués dans les cancers pédiatriques. C’est l’objectif du réseau national de recherche fondamentale et translationnelle React4Kids\, lancé en 2018 avec une dizaine de chercheurs et qui compte aujourd’hui plus de 380 membres. »\nElle pilote également depuis 2020 la plateforme Share4Kids\, dont l’objectif est de mettre à disposition de la communauté scientifique des données multi-omiques de qualité en open-access sur les cancers des enfants.
URL:https://www.crct-inserm.fr/evenement/conference-bmp2-and-bmp7-cooperate-with-h3-3k27m-to-promote-quiescence-and-invasiveness-in-pediatric-diffuse-midline-gliomas-marie-castets-crcl/
LOCATION:Salle Cazaux + Visio Teams
CATEGORIES:Animation scientifique
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