Team 15 : Signaling in Oncogenesis, Angiogenesis and Permeability

Research Projects

On the ground of our interests for molecular piracy exerted by tumor cells to survive, adapt and remodel their environment, we explore the signaling mechanisms involved in non-oncogene addiction and loss of vascular homeostasis.

1. Cell-Cell Interactions.
Within the tumor microenvironment, endothelial cells occupy a privileged exchange function with tumor cells, where they provide energy, oxygen, trophic factors and a direct access to bloodstream. We explore how cell-cell adhesion molecules enhance the physical and functional interactions between tumor cells and endothelial cells, favoring localized paracrine communication.

2. Intracellular Signaling and Post-Translational Modifications.
The tumor microenvironment is often characterized by an aberrant activation of the signaling pathway leading to the NF-KB transcription factor. Modulation of these cascades is notably finely regulated by ubiquitination, a reversible post-translational modification that corresponds to the covalent addition of ubiquitin chains. Our group is researching the impact of these modifications on cellular signaling and homeostasis.

3. Extracellular Communication and Vesicles.
Extracellular vesicles (EVs) are a preferred mode of communication between tumor cells and their microenvironment. These vesicles are detectable in the general circulation and their contents reflect the general state of the tumor, in particular responses to treatments. We examine the mechanisms of vesicle production and dissemination, as well as changes in their cargo.

Overall, our team combines cell biology and biochemistry approaches to identify new control points for tumor communication and thus characterize potentially relevant targets for the development of clinical treatments and diagnostic tools.

Staff

Julie Gavard, Researcher, Team leader (CNRS)
Nicolas Bidère, Researcher, Project leader (INSERM)
Gwennan André-Grégoire, Researcher (ICO)
Laëtitia Guével, University Lecturer (Nantes University)
Kilian Trillet, Engineer (INSERM)
Jane Jardine, Post-Doctoral Researcher
Carolina Nicolau, Post-Doctoral Researcher
Sara Rosinska, Post-Doctoral Researcher
Fiorella Spinelli, Post-Doctoral Researcher
An Thys, Post-Doctoral Researcher
Mathilde Kerhervé, PhD Student
Clément Maghe, PhD Student
Clotilde Renaud, PhD Student
Agnieszka Barbach, ERASMUS Student
Alya Zeinaty, Engineer Polytechnique
Luc Antigny, M2 Student
Yanis Mace, M2 Student
Mathilde Richard, M2 Student

Publications

– Thys A, Trillet K, Rosinska S, Gayraud A, Douanne T, Danger Y, Renaud CCN, Antigny L, Lavigne R, Pineau C, Com E, Vérité F, Gavard J, Bidère N. Serine 165 Phosphorylation of SHARPIN regulates the Activation of NF-κB. iScience 2020; 24(1): 101939. https://hal.archives-ouvertes.fr/hal-03099208
– Alves Nicolau C, Gavard J, Bidere N. TAK1 lessens the Activity of the Paracaspase MALT1 during T cell Receptor Signaling. Cell Immunol 2020; 353: 104115. https://www.hal.inserm.fr/inserm-02558368
– Jacobs KA, André-Grégoire G, Maghe C, Li Y, Thys A, Harford-Wright E, Trillet K, Douanne T, Frenel JS, Bidere N, Gavard J. Paracaspase MALT1 regulates glioma cell survival by controlling endo-lysosome homeostasis. EMBO J 2020: e102030. https://www.hal.inserm.fr/inserm-02395350v1
– Douanne T, André-Grégoire G, Trillet K, Thys A, Papin A, Feyeux M, Hulin P, Chiron D, Gavard J, Bidere N. Pannexin-1 limits the production of proinflammatory cytokines during necroptosis. EMBO Rep 2019: 20(10): e47840. https://www.hal.inserm.fr/inserm-02281304v1
– Douanne T, André-Grégoire G, Thys A, Trillet K, Gavard J, Bidère N. CYLD Regulates Centriolar Satellites Proteostasis by Counteracting the E3 Ligase MIB1. Cell Reports. 2019: 27(6): 1657-65. https://www.hal.inserm.fr/inserm-02128157
– Duarte A, André-Grégoire G, Trillet K, Thys A, Bidère N, Ribeiro-Silva A, Gavard J. Inhibition of mTOR in Head and Neck Cancer Cells Alters Endothelial Cell Morphology in a Paracrine Fashion. Mol Carcinogenesis. 2019; 58: 161-8. https://www.hal.inserm.fr/inserm-01908781v1
– Thys A, Douanne T, Bidere N. Post-translational Modifications of the CARMA1-BCL10-MALT1 Complex in Lymphocytes and Activated B-cell Like Subtype of Diffuse Large B-cell Lymphoma. Front Oncol. 2018; 8: 498. https://www.hal.inserm.fr/inserm-01908802v1
– Roux Q, Gavard J. Endothelial Cell-Cell Junctions in Tumor Angiogenesis. In: Marmé D. (eds) Tumor Angiogenesis. Springer, Cham doi.org/10.1007/978-3-319-3125-6_39-1
– André-Grégoire G, Bidère N, Gavard J. Temozolomide Affects Extracellular Vesicles Released by Glioblastoma Cells. Biochimie 2018; pii: S0300-9084(18)30041-5. https://www.hal.inserm.fr/inserm-01715956v1
– Jacobs KA, Gavard J. 3D endothelial migration. Methods Mol Biol. 2018; 1749: 51-58.
– Harford-Wright E, Gavard J. Apelin, the Devil Inside Brain Tumors. J Exp Neurosci 2018; 12: 1-3. https://www.hal.inserm.fr/inserm-01810684v1
– Harford-Wright E, Andre-Gregoire G, Jacobs KA, Treps L, Le Gonidec S, Leclair HM, Gonzalez-Diest S, Roux Q, Guillonneau F, Loussouarn D, Oliver L, Vallette FM, Foufelle F, Valet P, Davenport AP, Glen RC, Bidere N, Gavard J. Pharmacological targeting of apelin impairs glioblastoma growth. Brain. 2017; 140(11): 2939-54. http://www.hal.inserm.fr/inserm-01611131v1
– Treps L, Perret R, Edmond S, Ricard D, Gavard J. Glioblastoma stem-like cells secrete the pro-angiogenic VEGF-A factor in extracellular vesicles. J Extracell Ves. 2017; 1(6). http://www.hal.inserm.fr/inserm-01573268v1
– Jacobs KA, Harford-Wright E, Gavard J. Neutralizing gp130 interferes with endothelial-mediated effects on glioblastoma stem-like cells. Cell Death Diff. 2017; 24(2): 384. http://www.hal.inserm.fr/inserm-01444543v1
– Harford-Wright E, Bidere N, Gavard J. β-escin selectively targets glioblastoma-initiating cell identity to reduce cell viability. Oncotarget. 2016; 7(41): 66865-79. http://www.hal.inserm.fr/inserm-01385219
– Douanne T, Gavard J, Bidère N. The paracaspase MALT1 cleaves the LUBAC subunit HOIL1 during antigen receptor signaling. J Cell Sci. 2016; 129(9): 1775-80. http://www.hal.inserm.fr/inserm-01311283
– Treps L, Edmond S, Harford-Wright E, Galan-Moya EM, Schmitt A, Azzi S, Citerne A, Bidere N, Ricard D, Gavard J. Extracellular vesicle-transported Semaphorin3A promotes vascular permeability in glioblastoma. Oncogene. 2016; 35, 2615-23. http://www.hal.inserm.fr/inserm-01406334v1
– Dubois SM, Alexia C, Wu Y, Leclair HM, Leveau C, Schol E, Fest T, Tarte K, Chen Z, Gavard J, Bidere N. A catalytic-independent role for the LUBAC in NF-κB activation upon antigen receptor engagement and in lymphoma cells. Blood. 2014; 123(14): 2199-203.
– Azzi S, Smith SS, Dwyer J, Leclair HM, Alexia C, Hebda JK, Dupin N, Bidere N, Gavard J. YGLF motif in the Kaposi Sarcoma Herpes Virus G protein coupled receptor adjusts NF-κB activation and paracrine actions. Oncogene. 2014; 33(49): 5609-18. https://www.hal.inserm.fr/inserm-01078184v1
– Alexia C, Poalas K, Carvalho G, Zermili N, Dwyer J, Dubois SM, Hatchi EM, Cordeiro N, Smith SS, Castanier C, Le Guelte A, Wan L, Kang Y, Vazquez A, Gavard J, Arnoult D, Bidere N. The endoplasmic reticulum acts as a platform for ubiquitylated components of Nuclear Factor-κB signaling. Sci Signal. 2013; 6: ra79.
– Le Guelte A, Galan-Moya EM, Dwyer J, Treps L, Kettler G, Hebda JK, Dubois S, Auffray C, Chneiweiss H, Bidere N, Gavard J. Semaphorin 3A elevates endothelial cell permeability through PP2A inactivation. J Cell Sci. 2012; 125: 4137-46.
– Galan-Moya EM, Le Guelte A, Lima Fernandes E, Thirant C, Dwyer J, Bidere N, Couraud PO, Scott MG, Junier MP, Chneiweiss H, Gavard J. Secreted factors from brain endothelial cells maintain glioblastoma stem-like cell expansion through the mTOR pathway. EMBO Rep. 2011; 12(5): 470-6.

Main Fundings