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UMR1078
Genetics, functional genomics
and biotechnology

Applied cancerology and splicing - Axis directed by Laurent CORCOS

INTRODUCTION

Contacts


INTRODUCTION

Our ECLA (Splicing, Cancer, Lipids, Apoptosis) team, within the INSERM-University 1078 unit, develops two main research axes, linked to genetic and metabolic alterations that occur during cancer development.

Firstly, we study how blunting the cholesterol synthesis pathway can trigger cell apoptosis. The objective of these studies is to build a systems biology model that can be used to simulate apoptosis level in response to a given level of pathway blockade. These analyses are performed in collaboration with Dassault Bioinformatics systems. One of the perspectives is to determine the effect of combinations of statins and anticancer drugs. For instance, we have demonstrated that the combination of lovastatin and docetaxel results in a synergistic level of human gastric cancer cells apoptosis (patented). An animal model is being studied.
Secondly, we analyze transcriptome remodeling during the early steps (adenomatous polyps) of colon cancer progression in man. We study the mechanisms that lead to alternative pre-mRNA splicing, the controls exerted by epigenetic players, by micro-RNAs, and the coupling between transcription and splicing. The main objective is here to identify novel prognostic and/or predictive markers that characterize the early steps of colon cancer progression and, more recently, myeloproliferative and myelodisplastic syndromes.
Several additional projects are also developed, upon analyzing colon cancer stem cells, and the links between PET-Scan-derived images and transcriptome (in collaboration with the INSERM-university 1101 research unit).


The cholesterol pathway

Summary of the theme

Within the BioIntelligence framework (Dassault Bioinformatics Systems), we analyze the integrated response of cancer cell lines to blockade of the cholesterol synthesis pathway by statins, major lipid levels-reducing drugs that can also trigger cell death apoptosis in cancer cells. This blockade leads to desensitizing the cells to growth factors that normally activate proteins from the Ras, Rho, Rab, Rac, cdc42, (etc.) families. This activation requires a prenylation step, i.e. the post-translational addition of a C15 (farnesyl-pyrophosphate, FPP) or a C20 (geranyl-geranyl-pyrophosphate, GGPP) carbon chain produced as intermediary metabolites from the cholesterol synthesis pathway. As a response to statins and combinations of statins and anticancer agents, we analyze the consequences of pathway blockade upon determining the levels of several enzyme activities, those of FPP and GGPP, various mRNAs, proteins, the functional activation of Ras, Rho, etc., and apoptosis. Such quantitative data are incorporated in a bioinformatics model in order to simulate cellular and sub-cellular behaviors induced by the treatments.

People involved

Laurent Corcos, DR2, Inserm
Catherine Le Jossic-Corcos, MCU, UBO
Jean-Philippe Metges, PU-PH, University Hospital Brest
Danielle Arzur, TR, UBO

Collaborations

Elisabeth Pécou-Gambaudo, Dassault Systems, Sophia Antipolis


Gene expression analysis in stomach and colon cancers 

Summary of the theme

We analyze the expression and alternative pre-mRNA splicing of some genes involved in tumor development and in the response to targeted therapies, including anti-angiogenic therapies, both in cancer cells and in stomach and colon cancer fragments.

People involved


Laurent Corcos, DR2, Inserm
Catherine Le Jossic-Corcos, MCU, UBO
 

Collaborations

Michel Robaszkiewicz, University Hospital Brest
Laurent Doucet, University Hospital Brest

Cédric Le Maréchal, PU-PH, University Hospital Brest
GenoSplice technology, Evry
Pathology Department University Hospital, Brest
Gastro-enterology Department, University Hospital, Brest
Genomics Platform, Biosit Rennes


Cancer stem cells

Summary of the theme

We analyze, in digestive cancer stem cells, the expression and splicing of genes involved in cancer progression and in metastases, from established cancer cell lines, in order to identify new markers that would predict therapeutic responses and metastatic progression.

People involved

Laurent Corcos, DR2, Inserm
Catherine Le Jossic-Corcos, MCU, UBO

Collaborations

Pierre-François Cartron, Inserm U892 CRCNA, Nantes


Analysis of the effect of a combination of statins and taxanes on tumor growth in immuno-compromised mice 

Summary of the theme

In the STATAX project, we analyze the therapeutic effects of a combination of statins and anticancer agents in immuno-compromised mice bearing tumeurs from HGT-1 human gastric cancer cells. We have already demonstrated the efficacy of such an association in these cells in culture (patent). 

People involved

Laurent Corcos, DR2, Inserm
Catherine Le Jossic-Corcos, MCU, UBO

Collaborations

Kilian Trillet, CRCNA Nantes
Séverine Loisel, animal facility, UBO


Image analysis and prediction of the therapeutic response

Summary of the theme

We analyze PET-Scan images in the context of tumor progression in various cancers, including head and neck cancers.

People involved

Laurent Corcos, DR2, Inserm

Collaborations

Florent Tixier, university hospital (Poitiers)
Catherine Cheze-Le Rest, university hospital (Poitiers)
Dimitris Visvikis, Inserm UMR1101, UBO
Head & neck department, university hospital (Brest)
Radiotherapy department, university hospital (Brest)


Personnels impliqués

Laurent Corcos, DR2, Inserm
Catherine Le Jossic-Corcos, MCU, UBO

Collaborations

Pierre-François Cartron, Inserm U892 CRCNA, Nantes


"GRAMMY" ERA Per Med European Project  : InteGRAtive analysis of tuMor, Microenvironment, immunitY and patient expectation for personalized response prediction in Gastric Cancer

JOINT TRANSNATIONAL CALL FOR PROPOSALS (2019) FOR “PERSONALISED MEDICINE : MULTIDISCIPLINARY RESEARCH TOWARDS IMPLEMENTATION”


Le cancer gastrique (CG) est une maladie complexe qui représente la cinquième tumeur maligne la plus répandue dans le monde et la troisième cause de décès par cancer. Les CG sont très hétérogènes et affectent deux fois plus d'hommes que de femmes. La chimiothérapie associée à la chirurgie représente la norme de soins pour les CG de stade II à III, mais l'efficacité de tels traitements est encore limitée pour de nombreux patients. Il est donc impératif de développer une approche innovante visant à identifier de nouveaux marqueurs prédictifs, y compris déduits de la prise en compte de l'impact de l'environnement psychosocial et culturel de chaque patient. Nous défendons en effet l’idée que le style de communication, le degré d’acceptation du traitement par le patient, ainsi que l'interaction médecin-patient, peuvent influer sur la réponse au traitement, avec en particulier des écarts d’observance. L’intégration de différents niveaux d’informations, biologiques et psychosociales, est très prometteuse, même si elle est particulièrement difficile, pour identifier les liens entre les caractéristiques biologiques spécifiques de la maladie, la perception du patient et le pronostic. Notre consortium associant l’UMR1078, l’UMR1101 (SHS), le laboratoire OPTIMAG, le CHRU de Brest ainsi que 3 autres équipes européennes (italienne porteuse du projet, grecque et allemande) relève d’une excellente complémentarité pour développer cet ambitieux projet porté par l’Europe pour les 3 prochaines années.


Laurent CORCOS et Ghislaine Rolland-Lozachmeur.


Contacts

Thème dirigé par Laurent CORCOS

Laurent CORCOS (DR2, INSERM)
Tél : +33 (0)2 98 01 83 01
Fax : +33 (0)2 98 01 83 22
laurent.corcos@univ-brest.fr 

George ALZEEB (Doctorant projet GRAMMY)
Tél : 33 (0)2 98 01 64 67
george.alzeeb(at)univ-brest.fr 

Danielle ARZUR (TR, UBO)
Tél : +33 (0)2 98 01 64 55
danielle.arzur@univ-brest.fr

Catherine LE JOSSIC-CORCOS (MCU, UBO)
Tél : +33 (0)2 98 01 79 02
Fax : +33 (0)2 98 01 83 22
catherine.corcos@univ-brest.fr


Jean-Philippe METGES (PU-PH associé, CHRU)
Tél : +33 (0)2 98 22 33 95
Fax : +33 (0)2 98 22 33 23
jean-philippe.metges@chu-brest.fr

Anciens membres :

Photo

Team picture

Résumé

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Contact

Dr. Laurent Corcos

Inserm UMR 1078
Faculté de médecine et des sciences de la santé
22 rue Camille Desmoulins
CS 93837
29238 BREST Cedex 3
Tél : +33 (0)2 98 01 83 01
Fax : +33 (0)2 98 01 83 22
laurent.corcos(at)univ-brest.fr