Team
Julie Guillermet-Guibert

SigDYN :

Integrated cellular signalling and PI3K isoforms

the specifities

of our research axis

 

The team directed by J Guillermet-Guibert studies the family of lipid kinases known as phosphoinositide 3-kinases (PI3Ks) from different angles. This family of enzymes is involved in major cellular functions such as cell survival, proliferation, growth, migration, differentiation but also protein synthesis and intracellular vesicular trafficking. In vertebrates, the PI3K family is divided into three different classes. This classification is based on their structure, mode of activation and lipid substrate specificity in vitro and in vivo. These enzymes, encoded by 8 different genes, all phosphorylate the hydroxyl group in position 3 of the inositol ring of phosphoinositides, hence their name.

Only class I (composed of PI3Kα, PI3Kβ, PI3Kγ, PI3Kδ) can convert phosphatidylinositol (4,5)-bisphosphate [PtdIns-4,5-P2, PtdIns (4,5) P2, PIP2] to phosphatidylinositol (3,4,5)-trisphosphate [PtdIns-3,4,5-P3, PtdIns (3,4,5) P3, PIP3]. The substrate of class I enzymes is mainly located at the cell membrane. Thus, activation of class I PI3Ks produces a lipid second messenger at the plasma membrane at the interface with the cytoplasm, which allows the transmission of biochemical information into the cytoplasm and leads to a cellular response.

Class II (PI3KC2α, PI3KC2β, PI3KC2γ) and class III (VPS34) PI3Ks can generate phosphatidylinositol 3-phosphate [PtdIns-3-P, PtdIns (3) P, PI-3-P]. Class II PI3Ks can also synthesise phosphatidylinositol (3,4)-bisphosphate [PtdIns-3, 4-P2, PtdIns (3,4) P2]. The substrates of these enzymes are present in the outer membranes of organelles within the cell, at the level of endosomes, autophagosomes. Thus, class II and III PI3Ks control intracellular vesicular trafficking.

The high activation of class I PI3Ks is considered to be a characteristic of cancer; however, the role of each class I PI3K in the different stages of carcinogenesis is poorly understood. This research is carried out by our team.

The roles of class II and III PI3Ks in cancer are poorly studied. We have undertaken to understand them.

We mostly apply our research to solid cancers such as pancreatic cancer to better understand, earlier diagnose and treat this deadly disease. We also work on ovarian cancers and collaborate with teams working on liquid cancers.

 

Oncogenic signalling

PI3K

Targeted therapies

résistance

Tumour niche

Cancer initiation

Mechanobiology

compression

Genetically modified mice

Tumour imaging

Pancreatic cancer

Ovarian cancer

RESEARCH PROJECTS

SCIENTIFIC PRODUCTIONS

PUBLICATIONS 2022
PUBLICATIONS 2021
Di-Luoffo, M., Z. Ben-Meriem, P. Lefebvre, M. Delarue, and J. Guillermet-Guibert. “PI3K Functions as a Hub in Mechanotransduction.” Trends in Biochemical Sciences 46, no. 11 (November 2021): 878–88. https://doi.org/10.1016/j.tibs.2021.05.005.
Cayron, C., S. Rigal, and J. Guillermet-Guibert. “Is Targeting Autophagy a Promising Lead to Unveil the Cloak of Invisibility in Pancreatic Cancer?” Clinics and Research in Hepatology and Gastroenterology 45, no. 6 (November 2021): 101622. https://doi.org/10.1016/j.clinre.2021.101622.
Cintas, Celia, Thibault Douche, Zahra Dantes, Emmanuelle Mouton-Barbosa, Marie-Pierre Bousquet, Coralie Cayron, Nicole Therville, et al. “Phosphoproteomics Identifies PI3K Inhibitor-Selective Adaptive Responses in Pancreatic Cancer Cell Therapy and Resistance.” Molecular Cancer Therapeutics, September 22, 2021, molcanther.0981.2020. https://doi.org/10.1158/1535-7163.MCT-20-0981.
Thibault, Benoit, Fernanda Ramos-Delgado, Elvire Pons-Tostivint, Nicole Therville, Celia Cintas, Silvia Arcucci, Stephanie Cassant-Sourdy, et al. “Pancreatic Cancer Intrinsic PI3Kα Activity Accelerates Metastasis and Rewires Macrophage Component.” EMBO Molecular Medicine 13, no. 7 (July 7, 2021): e13502. https://doi.org/10.15252/emmm.202013502.
Arcucci, Silvia, Fernanda Ramos-Delgado, Coralie Cayron, Nicole Therville, Marie-Pierre Gratacap, Céline Basset, Benoit Thibault, and Julie Guillermet-Guibert. “Organismal Roles for the PI3Kα and β Isoforms: Their Specificity, Redundancy or Cooperation Is Context-Dependent.” The Biochemical Journal 478, no. 6 (March 26, 2021): 1199–1225. https://doi.org/10.1042/BCJ20210004.
Mazloumi Gavgani, Fatemeh, Thomas Karlsson, Ingvild L. Tangen, Andrea Papdiné Morovicz, Victoria Smith Arnesen, Diana C. Turcu, Sandra Ninzima, et al. “Nuclear Upregulation of Class I Phosphoinositide 3-Kinase P110β Correlates with High 47S RRNA Levels in Cancer Cells.” Journal of Cell Science 134, no. 3 (February 10, 2021). https://doi.org/10.1242/jcs.246090.
PUBLICATIONS 2020
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
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.

team members

Julie Guillermet-Guibert
Chercheur / Researcher
Marlène Dufresne
Chercheur / Researcher
Nicole Therville
Ingénieur ou technicien / Engineer or Technician
Benoît Thibault
Chercheur / Researcher
Mickael Di-Luoffo
Chercheur / Researcher
Camille Guyon
Etudiant ou stagiaire / PhD student or Trainee
Coralie Cayron
Etudiant ou stagiaire / PhD student or Trainee

PARTERNSHIPS & FUNDING

Centre de Recherches en Cancérologie de Toulouse

Centre de Recherches en Cancérologie de Toulouse (Oncopole)

Toulouse – FR

Nous contacter

05 82 74 15 75

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