It is a true honor to have this opportunity to share our results at such a prestigious meeting again. If you are around, please come to my talk (OS05.7.A), see @valentino-ribecco.bsky.social presentation (OS03.6.A), and stop by Juliette Reveilles (P02.09.B) and Adrien Thomas' (P04.12.A) posters.

You can dive into all the multi-omics data and findings in the full paper.
Read more: doi.org/10.1093/neuo....
🧵 (9/9)

🙏 This research wouldn’t have been possible w/o the work of Oceane Anezo, Jeremy Raymond, Alberto Ballestín, Cathy Pichol-Thievend, Juliette Reveilles, Adrien Thomas, @valentino-ribecco.bsky.social, and the collaboration with Celine Vallot, @ggargiul.bsky.social , Vidhya M. Ravi, Kevin Joseph (7/9)

🎉 Huge congrats to Guillaume Bourmeau, leading author and my brilliant PhD student, for spearheading this work on GBM hybrid cells at @institutcurie.bsky.social! Your dedication made this breakthrough possible. (6/9)
#ProudPI,

🚀 Here's the exciting part: we can target this vulnerability.
We hit them with importazole (import blocker) and selinexor (export inhibitor).
🔥 Targeting nuclear import decreases the hybrid cell pool and enhances chemoradiation sensitivity, opening a new therapeutic avenue against GBM. (5/9)

🛡️ Therefore, these cells are resistant to treatment and are linked to a poorer patient prognosis. Using RNA-seq, nuclear proteome and scChIP-Seq, we discovered their Achilles' heel: a hyperactive nuclear transport system they rely on to import oncogenes like MYC and maintain their state. (4/9)

🤯 These hybrid cells don’t just look different, they proliferate like they’re on Red Bull and shrug off DNA damage after irradiation. Have they got superhuman repair skills? 🙄 (3/9)

🔬 Using dual fluorescent reporters for proneural & mesenchymal states, we tracked live patient-derived glioblastoma lines and uncovered a hybrid population expressing both signatures... let's talk about an identity crisis! (2/9)

𝗪𝗵𝘆 𝗱𝗼𝗲𝘀 𝘁𝗵𝗶𝘀 𝗺𝗮𝘁𝘁𝗲𝗿?
- Targeting Cx43-mediated EV signaling may limit GBM progression and aid therapeutic strategies.
- Surgical aspirate-derived EVs could help decode the tumor microenvironment and act as predictive biomarkers, aiding in patient stratification and personalized GBM treatment. 5/5

Using patients' surgical aspirates, we found that only L-EVs from tumor cells—not immune cells—promote migration, especially in mesenchymal GBM cells. Blocking Cx43 reduces tumor migration, suggesting a potential therapeutic target to limit GBM dissemination. 4/5

Our results reveal that a specific population of large EVs (L-EVs), autocrinally released by tumor cells, and isolated from either patient-derived cell lines or surgical aspirates, promotes tumor invasiveness through Connexin 43-Gap Junctions (Cx43-GJ) and PYK2 activation. 3/5

Carried out at Humanitas Research in the 𝗣𝗵𝗮𝗿𝗺𝗮𝗰𝗼𝗹𝗼𝗴𝘆 𝗮𝗻𝗱 𝗕𝗿𝗮𝗶𝗻 𝗣𝗮𝘁𝗵𝗼𝗹𝗼𝗴𝘆 𝗹𝗮𝗯𝗼𝗿𝗮𝘁𝗼𝗿𝘆 directed by Prof. Michela Matteoli at Humanitas University, our work reveals how 𝙀𝙭𝙩𝙧𝙖𝙘𝙚𝙡𝙡𝙪𝙡𝙖𝙧 𝙫𝙚𝙨𝙞𝙘𝙡𝙚𝙨 (𝙀𝙑𝙨) 𝙧𝙚𝙡𝙚𝙖𝙨𝙚𝙙 𝙗𝙮 𝙜𝙡𝙞𝙤𝙗𝙡𝙖𝙨𝙩𝙤𝙢𝙖 𝙘𝙚𝙡𝙡𝙨 𝙙𝙧𝙞𝙫𝙚 𝙩𝙪𝙢𝙤𝙧 𝙞𝙣𝙫𝙖𝙨𝙞𝙫𝙚𝙣𝙚𝙨𝙨 𝙫𝙞𝙖 𝘾𝙤𝙣𝙣𝙚𝙭𝙞𝙣-43 (𝘾𝙭43) 𝙜𝙖𝙥 𝙟𝙪𝙣𝙘𝙩𝙞𝙤𝙣𝙨. 2/5