CONTACT

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

See Pr. Puisieux's Biography

Cheney D - 2nd floor
Centre Léon Bérard
28 rue Laennec
69373 Lyon Cedex 08
France
ALBARET Marie-Alexandra
Senior Researcher, Centre Léon Bérard

marie.albaret@lyon.unicancer.fr

ANGILERI Francesca
Post-doctoral researcher

francesca.angileri@lyon.unicancer.fr

ARNAUD Ophélie
Post-doctoral researcher

ophelie.arnaud@lyon.unicancer.fr

BERTHEL Elise
Post-doctoral researcher

elise.berthel@inserm.fr

BOESPFLUG Amélie
BRAHMI Medhi
BRITEL Manon
CANET Aurélien
CARAMEL Julie
Senior researcher (CRCN), Inserm

julie.caramel@lyon.unicancer.fr

CHASSOT Christelle
Lab technician, Centre Léon Bérard

christelle.chassot@lyon.unicancer.fr

COLIN Catherine
Physician, Hospices Civils de Lyon

catherine.colin@chu-lyon.fr

DALLE Stéphane
Professor and Hospital Practitioner, Université Lyon 1 / Hospices Civils de Lyon

stephane.dalle@chu-lyon.fr

DE BLANDER Hadrien
DE LA FOUCHARDIERE Arnaud
Physician, Centre Léon Bérard

arnaud.delafouchardiere@lyon.unicancer.fr

DE SOUZA Geneviève
Lab technician, Centre Léon Bérard

genevieve.desouza@lyon.unicancer.fr

DEVIC Clément
DEVOUASSOUX-SHISHEBORAN Mojgan
Professor and Hospital Practitioner, Université Lyon 1 / Hospices Civils de Lyon

mojgan.devouassoux@chu-lyon.fr

FAUVET Frédérique
Engineer, Centre Léon Bérard

frederique.fauvet@lyon.unicancer.fr

FERLAZZO Mélanie
Post-doctoral researcher

melanie.ferlazzo@inserm.fr

FORAY Nicolas
Senior researcher (DR2), Inserm

nicolas.foray@inserm.fr

GRANZOTTO Adeline
Assistant engineer, Inserm

adeline.granzotto@inserm.fr

GRIMONT Maxime
Assistant engineer, Inserm

maxime.grimont@lyon.unicancer.fr

HOULIER Aurélie
JACQUEROUD Laurent
Post-doctoral researcher

laurent.jacqueroud@lyon.unicancer.fr

KARANIAN Marie
LACHUER Joël
Professor, Université Lyon 1

joel.lachuer@univ-lyon1.fr

LANGRY Marine
Lab technician, Centre Léon Bérard

marine.langry@lyon.unicancer.fr

LAVERGNE Vincent
Post-doctoral researcher

vincent.lavergne@lyon.unicancer.fr

LEONCE Camille
LIGIER Maud
MALET Lucie
MARTEAU Solène
MARTINEZ Pierre
Senior researcher (CRCN), Inserm

pierre.martinez@lyon.unicancer.fr

MASSE Ingrid
Lecturer, Université Lyon 1

ingrid.masse@lyon.unicancer.fr

MOREL Anne-Pierre
Senior researcher, Centre Léon Bérard

annepierre.morel@lyon.unicancer.fr

MOYRET-LALLE Caroline
Professor, Université Lyon 1

caroline.moyret-lalle@lyon.unicancer.fr

ORTIZ-CUARAN Sandra
Post-doctoral researcher

sandra.ortiz-cuaran@lyon.unicancer.fr

OUZOUNOVA Maria
Senior researcher (CRCN), CNRS

maria.ouzounova@lyon.unicancer.fr

PAYEN-GAY Léa
Professor and Hospital Practitioner, Université Lyon 1 / Hospices Civils de Lyon

lea.payen@univ-lyon1.fr

PERRIN Virginie
Engineer, Centre Léon Bérard

virginie.perrin@yon.unicancer.fr

POMMIER Roxane
Post-doctoral researcher

roxane.pommier@lyon.unicancer.fr

PUISIEUX Alain
Professor and Hospital Practitioner, Université Lyon 1 / Hospices Civils de Lyon

alain.puisieux@lyon.unicancer.fr

RUBY Samia
Senior researcher (CRCN), Inserm

samia.ruby@lyon.unicancer.fr

SAINTIGNY Pierre
Physician, Centre Léon Bérard

pierre.saintigny@lyon.unicancer.fr

SANLAVILLE Amélien
Post-doctoral researcher, Lab manager and Scientific writer

amelien.sanlaville@lyon.unicancer.fr

SERRE Laurent
Post-doctoral researcher

laurent.serre@lyon.unicancer.fr

SONZOGNI Laurène
Assistant Engineer, Centre Léon Bérard

laurene.sonzogni@inserm.fr

SWALDUZ Aurélie
Physician, Centre Léon Bérard

aurelie.swalduz@lyon.unicancer.fr

THOMAS Luc
Professor and Hospital Practitioner, Université Lyon 1 / Hospices Civils de Lyon

luc.thomas@lyon.unicancer.fr

TIRODE Franck
Senior researcher (DR2), Inserm

franck.tirode@lyon.unicancer.fr

TISSIER Agnès
Senior researcher (CRCN), Inserm

agnes.tissier@lyon.unicancer.fr

VIGNERON Arnaud
Lecturer, Université Lyon 1

arnaud.vigneron@lyon.unicancer.fr

WIERINCKX Anne
Lecturer, Université Lyon 1

anne.wierinckx@univ-lyon1.fr

Voir les objectifs et projets Voir les publications

Collaborations
- Frederic Hollande, Victorian Comprehensive Cancer Centre, University of Melbourne, Australia. Creation of an International Associated Laboratory (LIA, INSERM/CNRS) in 2017.

- Emmanuelle Charafe-Jauffret and Christophe Ginestier, Cancer Research Centre of Marseille, France.

- Eugene Tulchinsky, Leicester Cancer Research Centre, UK.

- Thomas Brabletz, University Erlangen, Germany.

- Christoph Klein, University of Regensburg, Germany.

- Jean-Sébastien Hoffmann, Cancer Research Centre of Toulouse, France.

Grants

- Institut National du Cancer
- Ligue nationale contre le Cancer, équipe labellisée
- Fondation ARC
- Fondation pour la Recherche Médicale
- Joint transnational call TRANSCAN

WORK GROUPS

Alain Puisieux, Professor and Hospital Practitioner, Team Leader

Breast Group
    Melanoma Group

    Lung, Head and Neck Group

    Sarcoma Group

    Radiobiology Group

OBJECTIVES

The plasticity of cancer cells underlies their capacity to adapt to the numerous selective pressures they encounter from tumor initiation to metastatic spread. At the crux of this concept is the epithelial-mesenchymal transition (EMT). EMT is a latent embryonic transdifferentiation program that turns polarized epithelial cells into motile mesenchymal ones. In human cancers of epithelial origin, EMT commitment has primarily been implicated in cancer cell invasion and metastatic spread. Our observations further highlight the role of EMT-inducing transcription factors (EMT-TFs) of the TWIST and ZEB families in the initiation and the development of primary tumors, including neuroblastomas, breast cancers and melanomas. Consistent with this notion, we have shown that EMT commitment endows cancer cells with stemness properties and that EMT-TFs inhibit the p53- and Rb-dependent oncosuppressive pathways and cooperate with mitogenic oncoproteins to foster malignant transformation in vitro and in vivo. Their oncogenic functions are dependent on their modulatory role on cell differentiation, EMT-TFs displaying either oncosuppressive or oncogenic activities in neural-crest cell-derived melanocytes according to their impact on MITF-driven differentiation programs. Of utmost importance, EMT has been shown in vitro and in vivo to confer tumour aggressiveness and resistance to both conventional and targeted therapies. Targeting EMT-driven tumour cell plasticity may therefore represent an innovative approach for cancer therapy.

PROJECT

Recently, we have demonstrated that EMT-TFs are expressed in normal mammary stem cells and that their expression influences the entire natural history of breast tumourigenesis. Indeed, unlike differentiated cells, human mammary stem cells have the innate capacity to withstand an aberrant mitogenic activation. This property is based on an antioxidant program driven by ZEB1, a potent EMT-TF, and by the methionine sulfoxide reductase MSRB3, a ZEB1 transcriptional target. This pre-emptive program prevents the formation of oncogene-induced DNA damage, a major cause of genomic instability, and influences the emergence of cancer-associated events. Overall, these data suggest that malignant transformation of mammary stem cells does not hinge on genomic instability and indicate that intrinsic properties of the cell-of-origin dictate the genomic landscape of breast cancers. The aims of our team are: i) to characterize the oncogenic functions of EMT-TFs, ii) to decipher their respective roles in the early stages of tumorigenesis and their influence on the clonal dynamics of tumorigenesis, and iii) to determine the impact of their expression on resistance to anti-cancer therapies, including conventional chemotherapies, targeted therapies and immune therapies, with breast cancers and melanomas as priority tumor types. The ultimate objective is to design approaches promoting the blockade EMT-driven plasticity, with the goal to increase cancer cell sensitivity to anti-cancer therapeutics.


Subpopulations of normal mammary epithelial cells exhibit distinct early responses to an oncogenic event.
While differentiated cells undergo massive DNA damage, mammary stem cells can withstand aberrant mitogenic signaling through a pre-emptive program driven by ZEB1 and MSRB3. This specific behavior impacts the natural history of breast tumorigenesis by favoring malignant transformation in the absence of genomic instability (figure from Morel et al., Nat Med 2017).

MAIN PUBLICATIONS

Puisieux A, Pommier RM, Morel AP, Lavial F. Cellular pliancy and the multistep process of tumorigenesis. Cancer Cell, 33: 164-172, 2018.

Caramel J, Ligier M, Puisieux A. Pleiotropic Roles for ZEB1 in Cancer. Cancer Research, 78: 30-35, 2018.

Morel AP, Ginestier C, Pommier RM, Cabaud O, Ruiz E, Wicinski J, Devouassoux-Shisheboran M, Combaret V, Finetti P, Chassot C, Pinatel P, 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. Nature Medicine, 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*. *corresponding authors. ZEB1-mediated melanoma cell plasticity enhances resistance to MAPK inhibitors. EMBO Molecular Medicine, 8: 1143-1161, 2016.

Puisieux A, Brabletz T, Caramel J. Oncogenic roles of EMT-inducing transcription factors. Nature Cell Biology, 16: 488-494, 2014. Highly cited paper, top 1% of the academic field of Molecular Biology & Genetics.

Caramel J, Papadogeorgakis E, Hill L, Browne GJ, Richard G, Wierinckx A, Saldanha G, 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: 466-480, 2013.

Marcel V, Ghayad SE, Belin S, Therizols G, Morel AP, Solano-Gonzalez E, Vendrell JA, Hacot S, Mertani HC, Albaret MA, Bourdon JC, Jordan L, Thompson A, Tafer Y, Cong R, Bouvet P, Saurin JC, Catez F, Prats AC, Puisieux A, Diaz JJ. P53 acts as a safeguard of translational control by regulating fibrillarin and rRNA methylation in cancer. Cancer Cell, 24: 318-330, 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 breast cancer-stem cells through epithelial-mesenchymal transition. PLoS One, 3: e288, 2008. Highly cited paper, top 1% of the academic field of Clinical Medicine.

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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