Post by Donovan PINEAU

🧠 6 years of work… with one simple big question : What makes adult primary brain tumors (gliomas) so deadly—what really drives their malignant progression notably from low-grade to high-grade tumors? Super excited to share our discoveries in Molecular Oncology : https://lnkd.in/eGJBJG-g ! 🧪 How to study gliomas ? A new adult patient-derived glioma cell biobank closely reproducing patient context in vitro (showcased here but incoming incredible work driven by my teammate Leonor Garcia : https://lnkd.in/e4jrfkS6) ⚡ Developing assays to explore glioma cell biology, leading to a re-evaluation of endothelin signaling, previously thought pro-proliferative. Endothelin is widely expressed and known as one of the most potent vasoconstrictors in the body. Endothelin signals through EDNRA and EDNRB, members of GPCR family which are the largest and most diverse family of cell surface receptors, and among the most therapeutically targeted. 🧬 In glioma, EDNRB is predominantly expressed in gliomas, while EDNRA is restricted to a perivascular tumor subpopulation in glioblastomas. ⚡ Through EDNRB activation, endothelin reveals a paradoxical role: ↓ proliferation BUT ↑ migration and tumor plasticity, associated with poor prognosis and called Proneural-to-Mesenchymal transition. 🔬 Deciphering EDNRB signaling in native conditions without transfection (HTRF, ratiometric probes): Pathways involved include Ca²⁺ | K⁺ | ERK | STAT3 ⚖️ Endothelin signaling as a tumor microenvironment–dependent process shaped by endothelial cells, BMP, inflammatory cytokines, Hippo/YAP1, Notch signaling, and hypoxia. 💥 Key insight: glioma cells don’t just grow — they adapt, move, and transform. 🧩 Bottom line: endothelin has a dual role in brain tumor progression 🚀 A step toward more realistic glioma models and better therapeutic thinking. Many thanks to all co-workers especially Leonor Garcia (see that fantastic graphical abstract) and the support from my supervisor and mentor jean philippe hugnot ! Hugo Arnold, Antonija Hanžek, Maialen Arrieta Lobo, Laurent R. Gauthier, Christine Granotier-Beckers, François D Boussin, Amaury HERBET, Hautiere Marie, Valentin Asei-Ceschino, Clémentin JACQUES, Laura Brard, @Thomas Harnois, Valérie Coronas, Bruno Constantin, Aurélien Chatelier, @Jean Chemin, Serge Urbach, Martial Séveno, @Szimonetta Hideg, Chantal Ripoll, Kasandra Aguilar Cázarez, @Min Zheng , @Guo-hao Huang, @Sheng-Qing Lv, @Lei Zhang, Philippe Rondard, Laurent Prezeau, Jean Philippe Pin, @Hugues Duffau, @Luc Bauchet, Valérie Rigau, Franck DENAT, Charles TRUILLET, Didier BOQUET Thanks to Institut de Génomique Fonctionnelle - IGF !