CONTACT

Alain PUISIEUX
CRCL
director
alain.puisieux
@lyon.unicancer.fr
+33 4 78 78 27 81
(assistant)

Cheney D - 2nd floor
Centre Léon Bérard
28 rue Laennec
69373 Lyon Cedex 08
France
ALBARET Marie-Alexandra
Cadre biologiste CLB
marie.albaret@lyon.unicancer.fr
AMATA Murielle
ANGILERI Francesca
Chercheur Postdoctorant
francesca.angileri@lyon.unicancer.fr
ARNAUD Ophélie
Chercheur post-doctorant
Ophelie.ARNAUD@lyon.unicancer.fr
BOESPFLUG Amélie
BRITEL Manon
CARAMEL Julie
COLIN Catherine
Praticien hospitalier HCL
catherine.colin@chu-lyon.fr
DALLE Stéphane
DE BLANDER Hadrien
DE LA FOUCHARDIERE Arnaud
DE SOUZA Geneviève
DEVERCHERE Julie
DEVIC Clément
DEVOUASSOUX Mojgan
FAUVET Frédérique
FERLAZZO Mélanie
FORAY Nicolas
MOYRET-LALLE Caroline
Professeur des Universités (UCBL)
caroline.moyret-lalle@lyon.unicancer.fr
FOY Jean-Philippe
GOMEZ Sophie
GRANZOTTO Adeline
GRIMONT Maxime
JACQUEROUD Laurent

Chercheur post-doctorant
laurent.jacqueroud@lyon.unicancer.fr

LACHUER Joël
LAMBERT Marie-Pierre
Chercheur post-doctorante
marie-pierre.lambert@lyon.unicancer.fr
LAMBLOT Christelle
MARTEAU Solène
MARTINEZ Pierre

Chercheur Post-Doctorant
pierre.martinez@lyon.unicancer.fr

MASSE Ingrid
MOREL Anne-Pierre
ORTIZ-CUARAN Sandra

Chercheur post-doctorante
Sandra.ORTIZ-CUARAN@lyon.unicancer.fr

OUZOUNOVA Maria
Chercheur Post-doctorante
maria.ouzounova@lyon.unicancer.fr
PAYEN-GAY Léa
PERRIN Virginie
POMMIER Roxane
Chercheur Post-doctorante
roxane.pommier@lyon.unicancer.fr
PRODHOMME Mélanie
PUISIEUX Alain
RUBY Samia
SAINTIGNY Pierre
Praticien hospitalier CLB
pierre.saintigny@lyon.unicancer.fr
SERRE Laurent
Chercheur post-doctorant
laurent.serre@lyon.unicancer.fr
SONZOGNI Laurène
SWALDUZ Aurélie
TIRODE Franck
TISSIER Agnès
VIGNERON Arnaud
WIERINCKX Anne
Voir les objectifs et projets Voir les publications

Collaborations

Dr Eugène Tulchinsky, Leicester University, Leicester, UK 
Pr Richard Marais, Institute of Cancer Research, London, UK 
Dr Douglas B. Spicer, University of the Main, Scarborough, USA 
Dr Lionel Larue, Institut Curie, Orsay, France 
Pr Pierre Laurent-Puig, Université Descartes, Paris 
Pr Ursula Hibner, Institut de Génétique Moléculaire, Montpellier, France 

Grants

Equipe labelisée par la Ligue Nationale contre le Cancer 
Institut National Contre de Cancer (INCa) 
Association pour la Recherche sur le Cancer (ARC) 
Equipe membre du « Laboratoire d’excellence » (Labex) DEVweCAN
Lyric

OBJECTIVES

The aim of our team consists of understanding how the aberrant activation of an embryonic transdifferentiation program, namely the epithelial-mesenchymal transition, frequently observed in human cancers, facilitates the tumour initiation. By studying the oncogenic properties of the key embryonic regulators and the cellular properties provided by EMT, we actually have demonstrated that EMT inducers and the associated transdifferentiation process affords cells an increased plasticity and an exacerbate sensitivity to micro-environmental changes, favouring thereby the escape of failsafe programs  and their malignant transformation. Deciphering the underlying mechanisms and developing strategies aimed at functionally neutralising these embryonic functions constitute our two main research axes.

PROJECT

The epithelial to mesenchymal transition (EMT) is a latent and reversible embryonic transdifferentiation process transiently providing epithelial cells with motility by converting them into mesenchymal ones. This program is regulated by a pleiad of signalling pathways that invariably converge to a limited number of transcription factors. Normally undetectable in a large majority of adult differentiated cells, these embryonic proteins are often aberrantly reactivated in cancers. As a reminiscence of their embryonic functions, by promoting EMT, they were found to promote cancer cell dissemination at the invasive fronts of tumours. We recently have demonstrated that they additionally alleviate the failsafe program induction (senescence and apoptosis) in response to oncogenic insults and thereby cooperate in vitro as well as in vivo with mitogenic proteins in promoting tumour development. The hijack of the embryonic process, likely through the associated  genetic reprogramming, also significantly accelerates cell transformation and dedifferentiation. These embryonic transcription factors therefore constitute key regulators of cell plasticity and important drivers of the neoplastic transformation.

 

 

Schematic representation of the interconnection between EMT and failsafe programs.
Reactivation of EMT-promoting embryonic transcription factors, induced in response to various stresses including hypoxia, mechanical constraints, and inflammatory responses, turns down the RB and p53 pathways. Through a positive feedback mechanism, EMT inducer expression is further enhanced, thus promoting EMT. Maintaining RB and p53 down-modulated is essential to generating a permissive environment for genetic and epigenetic reprogramming, providing cells with plasticity and adaptive properties. Unfortunately, these conditions constitute a favorable environment for tumor initiation.
Ansieau et al. Seminars in Cancer Biology 21: 392-397 (2011
)

 

The aims of our team consist of:

- further exploring the oncogenic properties of EMT-inducers and the associated transdifferentiation program. We aim in particular to assess their impact on the cellular metabolism as well as on pathways regulating cell plasticity and determination.

- examining a potential oncogenic cooperation between EMT inducers and mitogenic oncoproteins in additional tumour progression models, thanks to transgenic mouse models.

- evaluating the therapeutic interest of targeting EMT-inducers or EMT.

PUBLICATIONS

Morel AP, Ginestier C, Pommier RM, Cabaud O, Ruiz E, Wicinski J, Devouassoux-Shisheboran M, Combaret V, Finetti P, Chassot C, Pinatel C, Fauvet F, Saintigny P, Thomas E, Moyret-Lalle C, Lachuer J, Despras E, Jauffret JL, Bertucci F, Guitton J, Wierinckx A, Wang Q, Radosevic-Robin N, Penault-Llorca F, Cox DG, Hollande F, Ansieau S, Caramel J, Birnbaum D, Vigneron AM, Tissier A, Charafe-Jauffret E, Puisieux A. A stemness-related ZEB1-MSRB3 axis governs cellular pliancy and breast cancer genome stability. Nat Med, 23: 568-578, 2017.

Richard G, Dalle S, Monet MA, Ligier M, Boespflug A, Pommier RM, de la Fouchardière A, Perier-Muzet M, Depaepe L, Barnault R, Tondeur G, Ansieau S, Thomas E, Bertolotto C, Ballotti R, Mourah S, Battistella M, Lebbé C, Thomas L, Puisieux A, Caramel J. ZEB1-mediated melanoma cell plasticity enhances resistance to MAPK inhibitors. EMBO Mol Med., 8: 1143-1161, 2016.

Puisieux A, Brabeltz T, Caramel J. Oncogenic roles of EMT-inducing transcription factors. Nat Cell Biol, 16: 488-494, 2014.

Caramel J, Papadogeorgakis E, Hill L, Browne G, Richard G, Wierinckx A, Saldanha G, Osborne J, Hutchinson P, Tse G, Lachuer J, Puisieux A, Pringle JH, Ansieau S, Tulchinsky E. A switch in the expression of embryonic EMT-inducers drives the development of malignant melanoma. Cancer Cell 24, 1-15, 2013.

Morel A-P, Hinkal GW, Thomas C, Fauvet F, Courtois-Cox S, Wierinckx A, Devouassoux-Shisheboran M, Treilleux I, Tissier A, Gras B, Pourchet J, Puisieux I, Browne G, Spicer DB, Lachuer J, Ansieau S, Puisieux A. EMT inducers catalyze malignant transformation of mammary epithelial cells and drive tumorigenesis towards claudin-low tumors in transgenic mice. Plos Genetics, 8: e1002723, 2012.

Ansieau S, Bastid J, Doreau A, Morel AP, Bouchet BP, Thomas C, Fauvet F, Puisieux I, Doglioni C, Piccinin S, Maestro R, Voeltzel T, Selmi A, Valsesia-Wittmann S, Caron de Fromentel C, Puisieux A. Induction of EMT by twist proteins as a collateral effect of tumor-promoting inactivation of premature senescence. Cancer Cell, 14: 79-89, 2008.

Morel A-P, Lièvre M, Thomas C, Hinkal G, Ansieau S, Puisieux A. Generation of transformed mammary epithelial cells with stemness properties through epithelial-mesenchymal transition. PLoS ONE, 3: e2888, 2008.

Mehlen P, Puisieux A. Metastasis: a question of life or death. Nature Reviews Cancer, 6: 449-458, 2006.

Valsesia-Wittmann S, Magdeleine M, Dupasquier S, Garin E, Jallas AC, Combaret V, Krause A, Leissner P, Puisieux A. Oncogenic cooperation between H-Twist and N-Myc overrides failsafe programs in cancer cells. Cancer Cell, 6: 625-630, 2004.

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