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ÉVÉNEMENTS

  • 2ème Symposium IRCI / 21-23 Juin 2020

La seconde édition du Symposium International IRCI (Immune Responses in Cancer and Infection) a été reportée à juin 2021 à l'Espaces Charles Mérieux, ENS Lyon.

Coorganisé par des chercheurs du Centre de Recherche en Cancérologie de Lyon et du Centre International de Recherche en Infectiologie, cet événement rassemblera la communauté scientifique intéressée par les dernières avancées dans le domaine de l’immunologie des cancers et des infections.

Le programme scientifique est axé autour de 6 sessions thématiques et des interventions de 20 conférenciers invités de renommée internationale tels que le Pr. Harald Zur Hausen (DKFZ, Allemagne), Prix Nobel de Médecine 2008 et le Pr. Ruslan Medzhitov (Yale University, Etats-Unis).

Pour plus d'informations, rendez-vous sur : https://irci2021.insight-outside.fr/

DIVERS

DERNIÈRES PUBLICATIONS

  • Failed Apoptosis Enhances Melanoma Cancer CellAggressiveness

Triggering apoptosis remains an efficient strategy to treat cancer. However, apoptosis is no longer a final destination since cancer cells can undergo failed apoptosis without dying. Recent evidence shows that limited mitochondrial permeabilization and non-lethal caspase activation occur under certain circumstances, although it remains unclear how failed apoptosis affects cancer cells. Using an original cancer cell model to trigger non-lethal caspase activation, we find that melanoma cancer cells undergoing failed apoptosis have a particular transcriptomic signature associated with focal adhesions, transendothelial migration, and modifications of the actin cytoskeleton. In line with this, cancer cells surviving apoptosis gain migration and invasion properties in vitro and in vivo. We further demonstrate that failed apoptosis-associated gain in invasiveness is regulated by the c-Jun N-terminal kinase (JNK) pathway, whereas its RNA sequencing signature is found in metastatic melanoma. These findings advance our understanding of how cell death can both cure and promote cancer. 

  • Netrin-1 promotes naive pluripotency through Neo1 and Unc5b co-regulation of Wnt and MAPK signalling

In mouse embryonic stem cells (mESCs), chemical blockade of Gsk3α/β and Mek1/2 (2i) instructs a self-renewing ground state whose endogenous inducers are unknown. Here we show that the axon guidance cue Netrin-1 promotes naive pluripotency by triggering profound signalling, transcriptomic and epigenetic changes in mESCs. Furthermore, we demonstrate that Netrin-1 can substitute for blockade of Gsk3α/β and Mek1/2 to sustain self-renewal of mESCs in combination with leukaemia inhibitory factor and regulates the formation of the mouse pluripotent blastocyst. Mechanistically, we reveal how Netrin-1 and the balance of its receptors Neo1 and Unc5B co-regulate Wnt and MAPK pathways in both mouse and human ESCs. Netrin-1 induces Fak kinase to inactivate Gsk3α/β and stabilize β-catenin while increasing the phosphatase activity of a Ppp2r2c-containing Pp2a complex to reduce Erk1/2 activity. Collectively, this work identifies Netrin-1 as a regulator of pluripotency and reveals that it mediates different effects in mESCs depending on its receptor dosage, opening perspectives for balancing self-renewal and lineage commitment.

https://doi.org/10.1038/s41556-020-0483-2

  • Nature Communications

Hepatitis Delta Virus histone mimicry drives the recruitment of chromatin remodelers for viral RNA r

Hepatitis Delta virus (HDV) is a satellite of Hepatitis B virus with a single-stranded circular RNA genome. HDV RNA genome synthesis is carried out in infected cells by cellular RNA polymerases with the assistance of the small hepatitis delta antigen (S-HDAg). Here we show that S-HDAg binds the bromodomain (BRD) adjacent to zinc finger domain 2B (BAZ2B) protein, a regulatory subunit of BAZ2B-associated remodeling factor (BRF) ISWI chromatin remodeling complexes. shRNA-mediated silencing of BAZ2B or its inactivation with the BAZ2B BRD inhibitor GSK2801 impairs HDV replication in HDV-infected human hepatocytes. S-HDAg contains a short linear interacting motif (SLiM) KacXXR, similar to the one recognized by BAZ2B BRD in histone H3. We found that the integrity of the S-HDAg SLiM sequence is required for S-HDAg interaction with BAZ2B BRD and for HDV RNA replication. Our results suggest that S-HDAg uses a histone mimicry strategy to co-activate the RNA polymerase II-dependent synthesis of HDV RNA and sustain HDV replication.

https://doi.org/10.1038/s41467-020-14299-9

  • Science Translational Medicine

Repurposing rotavirus vaccines for intratumoral immunotherapy can overcome resistance to immune checkpoint blockade.

Although immune checkpoint–targeted therapies are currently revolutionizing cancer care, only a minority of patients develop durable objective responses to anti–PD-1, PD-L1, and CTLA-4 therapy. Therefore, new therapeutic interventions are needed to increase the immunogenicity of tumors and overcome the resistance to these immunotherapies. Oncolytic properties of common viruses can be exploited for the priming of antitumor immunity, and such oncolytic viruses are currently in active clinical development in combination with immune checkpoint–targeted therapies.

> MORE INFORMATION

DOI: 10.1126/scitranslmed.aat5025

OFFRES D'EMPLOI

  • Juillet 2020 - Ingénieur d'étude

Dans le cadre d'un projet européen, l'équipe "Anticorps Anticancer" du CRCL et l'équipe "Gepharm" du LAGEPP recherchent un ingénieur d'étude en biologie cellulaire.
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  • July 2020 - Postdoctoral position

The laboratory of Prof Julien C. Marie is seeking an experienced, creative and autonomous post-doctoral fellow to study the effects of TGF-b on T cell-biology. A particular focus is proposed on deciphering mechanisms of action of TGF-b in controlling skin inflammation using both in vitro and in vivo mouse models.
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  • May 2020 - PhD Position

IMPORTANT : Vous devez obligatoirement postuler sur le site Portail Emploi CNRS

Financement doctoral CDD au CRCL H/F "caractérisation du rôle de netrin-1 dans la résistance et la plasticité des cancers" (équipe P. Mehlen)
 
Assurez-vous que votre profil candidat soit correctement renseigné avant de postuler. Les informations de votre profil complètent celles associées à chaque candidature. Afin d’augmenter votre visibilité sur notre Portail Emploi et ainsi permettre aux recruteurs de consulter votre profil candidat, vous avez la possibilité de déposer votre CV dans notre CVThèque en un clic ! 

  • January 2020 - Post-doctoral position

The laboratory of Dr. Julien C. Marie is seeking an experienced, creative and autonomous post-doctoral fellow to study the effects of TGF-B on T cell-biology.
More information

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