Équipe
Julie Guillermet-Guibert
SigDYN :
Signalisation cellulaire intégrée et isoformes de PI3K
Les spécificités
de notre axe de recherche
La famille des kinases lipidiques appelées phosphoinositide 3-kinases (PI3K) est impliquée dans des fonctions cellulaires majeures telles que la survie, la prolifération, la croissance, la migration, la différenciation cellulaire mais aussi la synthèse des protéines et le trafic vésiculaire intracellulaire. Chez les vertébrés, la famille PI3K est divisée en trois classes différentes. Cette classification est basée sur leur structure, leur mode d’activation et la spécificité de leur substrat lipidique in vitro et in vivo. Ces enzymes, codées par 8 gènes différents, phosphorylent le groupement hydroxyle en position 3 du noyau inositol des phosphoinositides, d’où leur nom.
Seule, la classe I (composée de PI3Kα, PI3Kβ, PI3Kγ, PI3Kδ) peut produire à partir du phosphatidylinositol (4,5) -bisphosphate [PtdIns-4,5-P2, PtdIns (4,5) P2, PIP2] du phosphatidylinositol (3,4,5) -trisphosphate [PtdIns-3,4,5-P3, PtdIns (3,4,5) P3, PIP3]. Le substrat des enzymes de classe I est majoritairement localisé à la membrane cellulaire. Ainsi, l’activation des PI3K de classe I produit un second messager lipidique à la membrane plasmique à l’interface avec le cytoplasme, ce qui permet la transmission de l’information biochimique dans le cytoplasme et qui conduit à une réponse cellulaire.
Les PI3K de classe II (PI3KC2α, PI3KC2β, PI3KC2γ) et de classe III (VPS34) peuvent générer du phosphatidylinositol 3-phosphate [PtdIns-3-P, PtdIns (3) P, PI-3-P]. Les PI3K de classe II peuvent aussi synthétiser le phosphatidylinositol (3,4) -bisphosphate [PtdIns-3, 4-P2, PtdIns (3,4) P2]. Les substrats de ces enzymes sont présents dans les membranes externes des organites à l’intérieur de la cellule, au niveau des endosomes, des autophagosomes. Ainsi, les PI3K de classe II et III contrôlent le trafic vésiculaire intracellulaire.
La forte activation des PI3K de classe I est considérée comme une caractéristique du cancer ; cependant, le rôle de chaque PI3K de classe I dans les différentes étapes de cancérogenèse est mal connu. Ces recherches sont réalisées par notre équipe.
Les rôles des PI3K de classe II et III dans le cancer sont très peu étudiés. Nous avons entrepris de les comprendre.
Signalisation oncogénique
PI3K
thérapies ciblées
résistance
niche tumorale
initiation du cancer
mécanobiologie
compression
souris génétiquement modifiées
imagerie des tumeurs
cancer du pancréas
cancer de l’ovaire
DES PROJETS
DE RECHERCHE
Mieux diagnostiquer et traiter avec les thérapies ciblées.
Dr C.Basset
Importance des isoformes de PI3K en physiopathologie
Dr B.Thibault
Importance des isoformes de PI3K comme intégrateur majeur de la mécanotransduction.
Dr M.Delarue et Dr M.Di-Luoffo
LES FOCUS
DE L’ÉQUIPE
Découvrir
Comprendre
Participer
En live
;
Maria Chaouki successfully presented her work at the SFH (société française d'hématologie) congress in Paris! She demonstrated the importance of limiting the dose of PI3K delta inhibitors to maintain efficacy and reduce toxicity in lymphoma.
PRODUCTIONS SCIENTIFIQUES
PUBLICATIONS 2025
7813506
PKLPPQDF
2025
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Despas, Fabien, Maria Chaouki, Sandra de Barros, Baptiste Bonneau, Ben Allal, Julie Guillermet-Guibert, and Loïc Ysebaert. “Pharmacokinetics of Idelalisib in Chronic Lymphocytic Leukemia and Follicular Lymphoma Disclose Better Outcomes for Patients with Lower Exposure.” Leukemia & Lymphoma 65, no. 9 (September 2024): 1378–80. https://doi.org/10.1080/10428194.2024.2353330.
Fébrissy, Chanaëlle, Marine Adlanmerini, Christel Péqueux, Frédéric Boudou, Mélissa Buscato, Adrien Gargaros, Silveric Gilardi-Bresson, et al. “Reprogramming of Endothelial Gene Expression by Tamoxifen Inhibits Angiogenesis and ERα-Negative Tumor Growth.” Theranostics 14, no. 1 (2024): 249–64. https://doi.org/10.7150/thno.87306.
PUBLICATIONS 2023
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2023
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https://www.crct-inserm.fr/wp-content/plugins/zotpress/
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Chaves-Almagro, Carline, Johanna Auriau, Alizée Dortignac, Pascal Clerc, Hubert Lulka, Simon Deleruyelle, Fabrice Projetti, et al. “Upregulated Apelin Signaling in Pancreatic Cancer Activates Oncogenic Signaling Pathways to Promote Tumor Development.” International Journal of Molecular Sciences 23, no. 18 (September 13, 2022): 10600. https://doi.org/10.3390/ijms231810600.
PUBLICATIONS 2021
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Rizzuti, Ilaria Francesca, Pietro Mascheroni, Silvia Arcucci, Zacchari Ben-Mériem, Audrey Prunet, Catherine Barentin, Charlotte Rivière, et al. “Mechanical Control of Cell Proliferation Increases Resistance to Chemotherapeutic Agents.” Physical Review Letters 125, no. 12 (September 18, 2020): 128103. https://doi.org/10.1103/PhysRevLett.125.128103.
Hakobyan, Davit, Chantal Médina, Nathalie Dusserre, Marie-Laure Stachowicz, Charles Handschin, Jean-Christophe Fricain, Julie Guillermet-Guibert, and Hugo Oliveira. “Laser-Assisted 3D Bioprinting of Exocrine Pancreas Spheroid Models for Cancer Initiation Study.” Biofabrication 12, no. 3 (April 16, 2020): 035001. https://doi.org/10.1088/1758-5090/ab7cb8.
Cayron, Coralie, and Julie Guillermet-Guibert. “The Type of KRAS Mutation Drives PI3Kα/γ Signalling Dependency: Implication for the Choice of Targeted Therapy in Pancreatic Adenocarcinoma Patients.” Clinics and Research in Hepatology and Gastroenterology, 2020, S2210740120301662. https://doi.org/10.1016/j.clinre.2020.05.021.
PUBLICATIONS 2019
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2019
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34955
https://www.crct-inserm.fr/wp-content/plugins/zotpress/
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Zamora, Audrey, Melinda Alves, Charlotte Chollet, Nicole Therville, Tiffany Fougeray, Florence Tatin, Camille Franchet, et al. “Paclitaxel Induces Lymphatic Endothelial Cells Autophagy to Promote Metastasis.” Cell Death & Disease 10, no. 12 (December 20, 2019): 956. https://doi.org/10.1038/s41419-019-2181-1.
Müller, David, Sauyeun Shin, Théo Goullet de Rugy, Rémi Samain, Romain Baer, Manon Strehaiano, Laia Masvidal-Sanz, et al. “eIF4A Inhibition Circumvents Uncontrolled DNA Replication Mediated by 4E-BP1 Loss in Pancreatic Cancer.” JCI Insight 4, no. 21 (November 1, 2019). https://doi.org/10.1172/jci.insight.121951.
Therville, Nicole, Silvia Arcucci, Aurélie Vertut, Fernanda Ramos-Delgado, Dina Ferreira Da Mota, Marlène Dufresne, Céline Basset, and Julie Guillermet-Guibert. “Experimental Pancreatic Cancer Develops in Soft Pancreas: Novel Leads for an Individualized Diagnosis by Ultrafast Elasticity Imaging.” Theranostics 9, no. 22 (2019): 6369–79. https://doi.org/10.7150/thno.34066.
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