Team 07 : Stress Adaptation and Tumor Escape

Team leader : Dr Philippe P Juin (lab director)

Research Projects

Our Team is based at IRS-UN in Nantes and ICO in Saint-Herblain. Our goal is to identify vulnerabilities and markers of aggressive cancers by exploring how individual, yet concerted, cell phenotypes contribute to progression and therapeutic resistance. We view tumor escape as resulting from the aberrant survival of malignant or non-malignant cells that adapt to diverse tumor related stresses. We consider that such adaptation has to be mapped to classify patients, and targeted to improve treatments. We focus our studies, albeit non exclusively, on breast cancers. Recent cell-by-cell descriptions showed high intratumoral heterogeneity of epithelial cells (of distinct types/states), at least partly favored by epithelial plasticity programs (such as Epithelial to Mesenchymal Plasticity- EMP) and co-evolving with a pro-tumoral cellular microenvironment. To explore how these pseudo-organs are built on “undead cells”, we address distinct themes, animated by specific research groups (encompassing scientists, students and technical staff supervised by a PI). The tight connections between groups are not only ensured by the complementarity between subjects but also by the partial mutualization of technical staff expert in molecular biology, ex vivo cultures derived from human samples or in vivo models, and by the sharing of bio-analytical approaches (led by dedicated scientists). One of the strengths of our team is that it brings together scientists with very diverse backgrounds going from cell biology to molecular biology with a clear attraction for innovation and new technologies. Our positioning at the interface of upstream research and transfer research allows us, by taking full advantage of the complementary expertise of the researchers, clinicians and veterinarians who constitute our team, to study samples derived from patients in addition to relevant models of cancer pathology.

How does plasticity contribute to pathogenic cell survival? Independently of any notion of oligoclonality, EMP (and possibly other programs) maintains intra-tumor heterogeneity through the dynamic induction of phenotypic conversions, and creates aggressive subpopulations within tumor ecotypes. The group  Cell Plasticity and Primary Cilia and disease (CP2C) supervised by V Guen investigates how hybrid E/M programs are associated with primary ciliogenesis, and how the latter contributes to survival, self-renewal, tissue regeneration and tumor relapse (Wilson, 2021). The pro-tumoral effects of EMP are further enhanced by the fact that it promotes a hybrid E/M state leading cell invasion and that the expression of vimentin, characteristic of this state, is necessary for invasion (Grasset 2022). The group Metastasis recently created by E Grasset further explores programs, such as EMP and Vimentin in particular that allow malignant cells to adapt to stress encountered during metastatic colonization, including the sequential steps of metastatic seeding and of outgrowth.

How do malignant cells survive despite tumor related stresses, in response to cytotoxic chemotherapy and/or immune checkpoint inhibition? Our studies of intrinsic regulation of cell survival are based on the notion that various stimuli during tumor progression (akin to these during morphogenesis) and most anti-cancer therapies alter mitochondrial integrity, which is tightly controlled by BCL-2 family proteins (Juin et al. 2013). The group BH3 supervised by L Maillet explores how these proteins engage into protein complexes to favor survival, how these complexes are regulated by novel partners (Vuillier, 2018) and how they are perturbed pharmacologically by BH3 mimetics (Pécot, 2016). A critical feature is the C-terminal mediated anchoring of these proteins at subcellular membranes such as the mitochondrial outer membrane, and we recently hinted that BCL-2 proteins might regulate mitochondrial scaffolding (Belaid, BioRxiv). The group Mitochondria supervised by L Lalier investigates how dynamic exchanges between these organelles and other subcellar compartments in response to stress contribute to adaptive survival (Lalier 2022, Mignard 2020).

Which intercellular communications contribute to aberrant cell survival? Recent atlases of breast cancers show that distinct epithelial states are close to specific non-malignant cell types. Cell compositions appear to follow ecotype rules that need to be understood with the characterization of how cells dialog with each other, and of extrinsic signals related to cell survival. The group Cancer Associated Fibroblasts and Apoptosis Resistance (CARE) supervised by F Souazé studies the influence of this major component of breast cancers on malignant cell survival (Louault, 2019), in treatment naïve and chemotherapy treated cancers, and seeks for vulnerabilities specifically associated with the pathological differentiation of these cells in the tumor microenvironment (Bonneaud, 2022). We recently established that the cytosolic DNA sensing pathway is activated in malignant cells by antimitotic agents (Lohard, 2020). The group Therapy Induced Cell Death (TICD) supervised by S Barillé-Nion investigates the dialog between malignant and immune cells in the context of therapy. Emphasizing our interconnected nature, this group is naturally led to study the different modes of cell death triggered by treatments, in coordination with the groups described above.

These studies are complemented by two transversal axis. The group Epigenetic, epitranscriptomic and transcriptomic reprogramming (Epi2TR) supervised by PF Cartron studies how base modifications in promoter regions and miRNAs regulate gene expression and cell survival, shape epithelial heterogeneity and influence intercellular communications. The pioneering identification of miRNA modifications (Cheray 2020) is of particular interest as modified miRNAs can be found in exosomes (contributing to horizontal information transfer) and in blood samples (as « epimarks » of treatment-induced counter-selections providing a window for measuring longitudinal evolutions, Briand, 2020). Our phenotypic characterizations rely on bulk and single cell RNA sequencing and the corresponding analytical needs (and related questions) are assumed by the development of state of the art bioinformatic approaches by F Gautier together with J Derrien (collab. Team 8), contributing to subjects apprehended by all groups. Along another transversal axis, we develop novel methodologies together with F Guillonneau and C Guette, headers of the proteomics group (PROTEO), for in depth proteomic characterizations of intracellular protein complexes, subcellular proteomes, soluble and exosomal proteins and tissue composition, in order to provide a fine grain description of breast cancers as cellular ecosystems shaped by stress responses.            
                                                                                     

Cancer Associated Fibroblasts (CAFs)                                                    "Organemone" by Floriane by immunocytochemistry

 

 

A big thanks to the Association Entraide Cancer Saint Nazaire for its support of our breast cancer research!

A big thank you to the Ligue contre le Cancer for its long term support of the SATE team to support its research on the identification of MCL-1 dependent compensatory mechanisms contributing to cellular heterogeneity in aggressive breast cancers

Philippe Juin, Winner of the Avenir 2022 Research Grant awarded by Association Ruban Rose for a project of collaboration between Team 7 and Team 12 on breast cancer Click here to watch the interview!

Congratulations to Vincent Guen, identified as a promising young researcher by the program "Etoiles Montantes" of the Region Pays de la Loire

  Have a look at our the lastest publication: Targeting of MCL-1 in breast cancer-associated fibroblasts
reverses their myofibroblastic phenotype and pro-invasive properties, please click on it  to read more

  Thanks to the patient association "Entraide Cancer 44" to support our research projects on breast cancer!

• Please click on this link to see our recent key publications

Director

Philippe P Juin, DR INSERM (HDR)

Researchers

Sophie Barillé-Nion, CR INSERM (HDR)
Pierre-François Cartron, CR INSERM (HDR)
Eloïse Grasset, CDD INSERM
Fabien Gautier, CR ICO
Vincent Guen, CR INSERM (HDR)
Catherine Guette, CR ICO
François Guillonneau, CR ICO
Lisenn Lalier, CR ICO
Magali Le Breton, Associated Professor 
Laurent Maillet, CR INSERM (HDR)
Frédérique Souazé, CR INSERM (HDR)

Technical and administrative staff

Quentin Batard, AI
Thomas Cabioch, TR
Gwenola Cartron, Project manager, ICO
Laurine Duarte, AI CDD
Dorian Espi-Bastien, TR CDD
Aurélie Fétiveau, TR
Philippine Giowachini, AI CDD
Arulraj Nadaradjane, TR
Thomas Pele, IE CDD
Julie Roul, TR

PhD students and Post docs

Laurine Berland, PhD student
Florian Chocteau, PhD student
Aurore Dupuy, PhD student
Chloé Lefebvre, PhD student
Camille Tessier, PhD student
Katherine Aquino-Matias, visiting PhD student
Alice Serafin, Post-doc
Hana Triki, Post-Doc

Medical associated staff

Mario Campone, PU-PH ICO
Mathilde Dupé, PH ICO
Jean-Sébastien Frenel, PU-PH ICO
Pascal Jézéquel, PH ICO
Olivier Kerdraon, PH ICO
Judith Raimbourg, PH ICO
Frédérique Nguyen, Associated professor ONIRIS
Marie Robert, PH ICO

 

• Wilson MM, Callens C, Le Gallo M, Mironov S, Ding Q, Salamagnon A, Chavarria TE, Viel R, Peasah AD, Bhutkar A, Martin S, Godey F, Tas P, Kang HS, Juin PP, Jetten AM, Visvader JE, Weinberg RA, Attanasio M, Prigent C, Lees JA, Guen VJ. An EMT-primary cilium-GLIS2 signaling axis regulates mammogenesis and claudin-low breast tumorigenesis. Sci Adv. 2021 Oct 29;7(44)
• Ben Azzouz F, Michel B, Lasla H, Gouraud W, François AF, Girka F, Lecointre T, Guérin-Charbonnel C, Juin PP, Campone M, Jézéquel P. Development of an absolute assignment predictor for triple-negative breast cancer subtyping using machine learning approaches. Comput Biol Med. 2021 Feb;129:104171.
• Lohard S, Bourgeois N, Maillet L, Gautier F, Fétiveau A, Lasla H, Nguyen F, Vuillier C, Dumont A, Moreau-Aubry A, Frapin M, David L, Loussouarn D, Kerdraon O, Campone M, Jézéquel P, Juin PP*, Barillé-Nion S.* STING-dependent paracriny shapes apoptotic priming of breast tumors in response to anti-mitotic treatment. Nat Commun. 2020 Jan 14;11(1):259.
• Jézéquel P, Patsouris A, Guette C, Juin PP, Campone M. RE: Immune checkpoint profiles in luminal B breast cancer (Commentary). J Natl Cancer Inst. 2020 Mar 19.
• Cheray M, Etcheverry A, Jacques C, Pacaud R, Bougras-Cartron G, Aubry M, Denoual F, Peterlongo P, Nadaradjane A, Briand J, Akcha F, Heymann D, Vallette FM, Mosser J, Ory B, Cartron PF. Cytosine methylation of mature microRNAs inhibits their functions and is associated with poor prognosis in glioblastoma multiforme. Mol Cancer. 2020 Feb 25;19(1):36
• Briand J, Sérandour AA, Nadaradjane A, Bougras-Cartron G, Heymann D, Ory B, Vallette FM, Cartron PF. N6-Adenosine Methylation of miRNA-200b-3p Influences Its Functionality and Is a Theranostic Tool. Mol Ther Nucleic Acids. 2020 Aug 14;22:72-83.
• Louault K, Bonneaud TL, Séveno C, Gomez-Bougie P, Nguyen F, Gautier F, Bourgeois N, Loussouarn D, Kerdraon O, Barillé -Nion S, Jézéquel P, Campone M, Amiot M, Juin PP*, Souazé F.* Interactions between cancer-associated fibroblasts and tumor cells promote MCL-1 dependency in estrogen receptor positive breast cancers. Oncogene. 2019 Apr;38(17):3261-3273.
• Vuillier C, Lohard S, Fétiveau A, Allègre J, Kayaci C, King LE, Braun F, Barillé-Nion S, Gautier F, Dubrez L, Gilmore AP, Juin PP*, Maillet L*. E2F1 interacts with BCL-xL and regulates its subcellular localization dynamics to trigger cell death. EMBO Rep. 2018 Feb;19(2):234-243.
• Carné Trécesson S, Souazé F, Basseville A, Bernard AC, Pécot J, Lopez J, Bessou M, Sarosiek KA, Letai A, Barillé -Nion S, Valo I, Coqueret O, Guette C,Campone M, Gautier F, Juin PP. BCL-X(L) directly modulates RAS signalling to favour cancer cell stemness. Nat Commun. 2017 Oct 24;8(1):1123.
• Pécot J, Maillet L, Le Pen J, Vuillier C, Carné Trécesson SC, Fétiveau A, Sarosiek KA, Bock FJ, Braun F, Letai A, Tait SWG, Gautier F*, Juin PP*. Tight Sequestration of BH3 Proteins by BCL-xL at Subcellular Membranes Contributes to Apoptotic Resistance. Cell Rep. 2016 Dec 20;17(12):3347-3358.

 

PARTNERSHIP	LABELS		FUNDINGS

CURRENT

Laurine Berland: EMBRAVE-TNBC: Exploring Mechanisms of Breast Cancer Metastasis through Epithelial-Mesenchymal Transition and Vimentin Expression in Triple-Negative Breast Cancer

Camille Tessier: Development of small-molecule inhibitors of primary ciliogenesis for research on primary cilia

Aurore Dupuy: Investigating the role of the primary cilium in mammary gland remodeling during the reproduction cycle

Chloé Lefebvre : Role of MCL-1 in myofibroblast phenotype and chemoresistance of fibroblasts associated with breast cancers

Florian Chocteau: Metastatic process in breast cancer after chemotherapy treatment:  Immune microenvironment and tumor clonal evolution in the metastatic niche

PAST

Alison Dumont: Heterogeneity in the response of breast tumors to antimitotics: What impacts on treatment resistance and immune response? Defense on December 11, 2023

Lisa Nocquet: Implication of BCL-xL and MCL-1 in the metabolic control of cell death by cancer-associated fibroblasts in triple negative breast cancer. Defense on November 30, 2023

Florestan Courant: Cross-species differences or similarities in epigenetic mechanisms induced by pesticides or chemotherapeutic agents. Defense on October 17, 2022

Nina Belaid: Modulation of KRAS activity by BCL-xL: mechanistic aspects and therapeutic implications. Defense on May 18, 2022

Thomas Bonneaud: Consequences of pharmacological targeting of MCL-1 on the myofibroblastic phenotype of breast cancer-associated fibroblasts. Defense on December 3, 2021

Margot Lavy: Regulating myeloid cell activity in tumors through Resolvlne receptors : chemR23. Defense on December 13, 2021

Manon Duforestel: Study of epigenetic mechanisms and dynamics in glioblastoma multiforme during the acquisition of temozolomide resistance.  Defense on September 17, 2021

Steven Lohard: STING-dependent paracriny shapes apoptotic priming of breast tumors in response to antimitotic treatment. Defense on May 3, 2019

Josephine Briand: Glioblastoma and epigenetics: from prevention to development of new treatments. Defense on December 12, 2019

Kevin Louault: Role of Cancer-associated fibroblast in apoptosis resistance in breast cancers. Defense on December 19, 2018

Céline Vuillier: Mitochondrial apoptosis regulated by E2F1. Involvement of the E2F1 mitochondrial targeting and interactions with the Bcl-2 Family anti-apoptotic members. Defense on December 19, 2016

Jessie Pécot: BCLxL dependence of cancer cells. Targeting of the dynamic BCLxL/PUMA/BAX network. Oncogenic pathways regulated by the non canonical RAS/BCLxL interaction (October 2015)

Eloise Véquaud: Study of mammary cancer cells response to silencing of surviving by RNA interference or pharmacological targeting: highlighting oh homologous recombination regulation by survivin. (December 2014)

From 2019
Morgan Zenatri 2023/24 : Master 2 Biologie-Santé, Nantes Université, France.
Angèle Palierne 2023/24 : Master 2 Biologie-Santé, Nantes Université, France. Etude des mécanismes cellulaires sous-jacents à la résistance aux traitements des cancers du sein induite par les fibroblastes du microenvironnement tumoral
Flavie Bernigole 2023/24 : Master 2 Génétique, Génomique et Biologie des Système, Nantes Université, France. Étude de l'hétérogénéité cellulaire dans la glande mammaire au cours du cycle de reproduction
Claire Lalevée 2023/24 : Master 2 Génétique, Génomique et Biologie des Système, Nantes Université, France. Analyse des profils cellulaires résistants par transcriptomique spatiale dans les cancers du sein réfractaires aux traitements
Audrey Roussel 2022/2023: M2 Biologie Moléculaire et Cellulaire Université de Rennes - Définir l'interactome de MCL-1 par BioID APEX
Mathilde Dupé 2022/23: Master 2 Biologie -Santé (Interactions Cellulaires et Applications Thérapeutiques ) University of Angers, France.Angers. Highlighting therapeutic opportunities induced by studying miRome reprogramming during the development of anastrozole resistance in endometrial cancer.
Aristide Massé 2022/23: Master2 BBRT, University of Nantes, France. Investigating the kinetics of MAM and the impact in the mitochondrial adaptation and resistance acquisition of cancer cells
Camille Tessier 2022/23 : Master 2 Biologie-Santé, Nantes Université, France. Investigating the role of epithelial plasticity and of primary cilia in breast cancer therapeutic resistance
Nicolas Balloud 2022/23: M2 BBRT  (Biologie Biotechnologie Recherche Thérapeutique) University of Nantes, France. Deciphering the epigenetic/epitranscriptomic reprogramming associated with acquisition of tolerance/resistance to targeted antitumor therapies
Aurore Dupuy 2021/22: Master 2 "Biologie Moléculaire et Cellulaire", University of Rennes 1, France. Investigating the role of the primary cilium in mammary gland remodeling during the reproduction cycle.
Maxime Richomme 2021/22: Master 2 BBRT, Nantes University
Klara Edern 2021/22: Equivalent Master 2 Bioinformatics at Ecole Centrale de Nantes "High throughput data analysis to predict tumor cell fate and/or the existence of therapeutic vulnerabilities"
Morgane Allory 2021/22: Master 2 Biologie Santé parcours "Interactions cellulaires et Application thérapeutiques",  Angers University.  Identification of epigentic and/or epitranscriptomic biomarkers predictive of vulnerabilities to drugs/targeted therapy molecules.
Chloé Lefebvre 2021/22: Master 2 "Biologie, Biotechnologie et Recherche Thérapeutique", Nantes University. Role of MCL-1 in myofibroblast phenotype and chemoresistance of fibroblasts associated with breast cancers.
Hugo Weber 2020/21: Master 2 « Oncologie Moléculaire et Biothérapies », Limoges University. Effect of irradiation on the sensitivity of CAFs and breast adenocarcinoma cancer cells to BH3 mimetics: Evaluation of their therapeutic potential as senolytic agents.
Yuna Landais 2020/2021: Equivalent Master 2 Bioinformatics at Ecole Centrale de Nantes. "Study of mitochondrial genome methylation by direct nanopore sequencing"
Elen Goujon 2020/2021: Equivalent Master 2 Bioinformatics at Ecole Centrale de Nantes. "Development of biomedical data analysis pipelines in oncology"
Piera Grisolina 2019/2020: ERASMUS. Master 2 "Biologie Moléculaire et Cellulaire" University of Rennes 1/Tieste University, Italy. Investigating the molecular mechanisms by which EMT programs induce primary ciliogenesis. 
Alison Dumont 2019/2020: Master 2 "Biologie, Biotechnologie et Recherche Thérapeutique", Nantes University: Induction of NOXA pro-apoptotic protein expression in response to Paclitaxel in breast tumors: Regulome analysis of its gene transcription.
Louis Paré 2019/2020: Equivalent Master 2 Bioinformatics at Ecole Centrale de Nantes. "Cinetic study of the resistance of anti-tumor treatments by epigenetic genome analysis"

2024

2022

 

• Courant F, Bougras-Cartron G, Abadie C, Frenel JS, Cartron PF. Modulation of DNA Methylation/Demethylation Reactions Induced by Nutraceuticals and Pollutants of Exposome Can Promote a C > T Mutation in the Breast Cancer Predisposing Gene PALB2. Epigenomes. 2022 Sep 30;6(4):32. doi: 10.3390/epigenomes6040032. PMID: 36278678
• Bonneaud TL, Lefebvre CC, Nocquet L, Basseville A, Roul J, Weber H, Campone M, Juin PP, Souazé F. Targeting of MCL-1 in breast cancer-associated fibroblasts reverses their myofibroblastic phenotype and pro-invasive properties. Cell Death Dis. 2022 Sep 14;13(9):787. doi: 10.1038/s41419-022-05214-9.
• Garnier D, Ratcliffe E, Briand J, Cartron PF, Oliver L, Vallette FM. The Activation of Mesenchymal Stem Cells by Glioblastoma Microvesicles Alters Their Exosomal Secretion of miR-100-5p, miR-9-5p and let-7d-5p. Biomedicines. 2022 Jan 6;10(1):112.
• Wilson MM, Callens C, Le Gallo M, Mironov S, Ding Q, Salamagnon A, Chavarria TE, Viel R, Peasah AD, Bhutkar A, Martin S, Godey F, Tas P, Kang HS, Juin PP, Jetten AM, Visvader JE, Weinberg RA, Attanasio M, Prigent C, Lees JA, Guen VJ. An EMT-primary cilium-GLIS2 signaling axis regulates mammogenesis and claudin-low breast tumorigenesis. Sci Adv. 2021 Oct 29;7(44):eabf6063. 
• Lalier L, Vallette F, Manon S. Bcl-2 Family Members and the Mitochondrial Import Machineries: The Roads to Death. Biomolecules. 2022 Jan 19;12(2):162. 

2021

• Lavy M, Gauttier V, Poirier N, Barillé-Nion S, Blanquart C. Specialized Pro-Resolving Mediators Mitigate Cancer-Related Inflammation: Role of Tumor-Associated Macrophages and Therapeutic Opportunities. Front. Immunol., 30 June 2021 | https://doi.org/10.3389/fimmu.2021.702785.
• Ben Azzouz F, Michel B, Lasla H, Gouraud W, François AF, Girka F, Lecointre T, Guérin-Charbonnel C, Juin PP, Campone M, Jézéquel P. Development of an absolute assignment predictor for triple-negative breast cancer subtyping using machine learning approaches. Comput Biol Med. 2021 Feb;129:104171. doi: 10.1016/j.compbiomed.2020.104171.
• Jézéquel P, Gouraud W, Ben Azzouz F, Guérin-Charbonnel C, Juin PP, Lasla H, Campone M. bc-GenExMiner 4.5: new mining module computes breast cancer differential gene expression analyses. Database (Oxford). 2021 Feb 18; 2021:baab007. doi: 10.1093/database/baab007.
• Tea I, De Luca A, Schiphorst AM, Grand M, Barillé-Nion S, Mirallié E, Drui D, Krempf M, Hankard R, Tcherkez G. Stable Isotope Abundance and Fractionation in Human Diseases. Metabolites. 2021 Jun 9;11(6):370. 
• Lalier L, Mignard V, Joalland MP, Lanoé D, Cartron PF, Manon S, Vallette FM. TOM20-mediated transfer of Bcl2 from ER to MAM and mitochondria upon induction of apoptosis. Cell Death Dis. 2021 Feb 15;12(2):182. 
• Wilson MM, Callens C, Le Gallo M, Mironov S, Ding Q, Salamagnon A, Chavarria TE, Viel R, Peasah AD, Bhutkar A, Martin S, Godey F, Tas P, Kang HS, Juin PP, Jetten AM, Visvader JE, Weinberg RA, Attanasio M, Prigent C, Lees JA, Guen VJ. An EMT-primary cilium-GLIS2 signaling axis regulates mammogenesis and claudin-low breast tumorigenesis. Sci Adv. 2021 Oct 29;7(44):eabf6063.
• Hazan R, Mori M, Danielian PS, Guen VJ, Rubin SM, Cardoso WV, Lees JA. E2F4's cytoplasmic role in multiciliogenesis is mediated via an N-terminal domain that binds two components of the centriole replication machinery, Deup1 and SAS6. Mol Biol Cell. 2021 Oct 1;32(20):ar1.
• Duclos M, Prigent C, Le Borgne R, Guen VJ. Three-Dimensional Imaging of Organoids to Study Primary Ciliogenesis During ex vivo Organogenesis. J Vis Exp. 2021 May 14;(171). 
• Olivier C, Oliver L, Lalier L, Vallette FM. Drug Resistance in Glioblastoma: The Two Faces of Oxidative Stress. Front Mol Biosci. 2021 Jan 27;7:620677.

2020

• Lohard S, Bourgeois N, Maillet L, Gautier F, Fétiveau A, Lasla H, Nguyen F, Vuillier C, Dumont A, Moreau-Aubry A, Frapin M, David L, Loussouarn D, Kerdraon O, Campone M, Jézéquel P, Juin PP, Barillé-Nion S. STING-dependent paracriny shapes apoptotic priming of breast tumors in response to anti-mitotic treatment. Nature Communications. 2020 11:259. doi.org/10.1038/s41467-019-13689-y
• Lohard S, Juin PP, Barillé-Nion S. Mitotic stress-induced secretome primes cancer cells to apoptosis and maximizes paclitaxel response in breast tumors when combined with BCL-xL-targeting BH3 mimetics. Mol Cell Oncol. 2020 Mar 19;7(3):1735912. doi: 10.1080/23723556.2020.1735912. 
• Barillé-Nion S, Lohard S, Juin PP: Targeting of BCL-2 Family Members during Anticancer Treatment: A Necessary Compromise between Individual Cell and Ecosystemic Responses? Biomolecules 2020 Jul 25;10(8):E1109. doi: 10.3390/biom10081109.
• Nocquet L, Juin PP, Souazé F. Mitochondria at Center of Exchanges between Cancer Cells and Cancer-Associated Fibroblasts during Tumor Progression. Cancers (Basel). 2020 Oct 17;12(10):3017. doi: 10.3390/cancers12103017.
• Guyon N, Garnier D, Briand J, Nadaradjane A, Bougras-Cartron G, Raimbourg J, Campone M, Heymann D, Vallette FM, Frenel JS, Cartron PF. Anti-PD1 therapy induces lymphocyte-derived exosomal miRNA-4315 release inhibiting Bim-mediated apoptosis of tumor cells. Cell Death Dis. 2020 Dec 11;11(12):1048. doi: 10.1038/s41419-020-03224-z.
• Peixoto P, Cartron PF, Serandour AA, Hervouet E. From 1957 to Nowadays: A Brief History of Epigenetics. Int J Mol Sci. 2020 Oct 14;21(20):7571. doi: 10.3390/ijms21207571. PMID: 33066397;
• Briand J, Sérandour AA, Nadaradjane A, Bougras-Cartron G, Heymann D, Ory B, Vallette FM, Cartron PF. N6-Adenosine Methylation of miRNA-200b-3p Influences Its Functionality and Is a Theranostic Tool. Mol Ther Nucleic Acids. 2020 Aug 14;22:72-83. doi: 10.1016/j.omtn.2020.08.010. 
• Oliver L, Lalier L, Salaud C, Heymann D, Cartron PF, Vallette FM. Drug resistance in glioblastoma: are persisters the key to therapy? Cancer Drug Resist. 2020 Aug 7;3(3):287-301. doi: 10.20517/cdr.2020.29.
• Briand J, Garnier D, Nadaradjane A, Clément-Colmou K, Potiron V, Supiot S, Bougras-Cartron G, Frenel JS, Heymann D, Vallette FM, Cartron PF. Radiotherapy-induced overexpression of exosomal miRNA-378a-3p in cancer cells limits natural killer cells cytotoxicity. Epigenomics. 2020 Mar;12(5):397-408. doi: 10.2217/epi-2019-0193. 
• Cheray M, Etcheverry A, Jacques C, Pacaud R, Bougras-Cartron G, Aubry M, Denoual F, Peterlongo P, Nadaradjane A, Briand J, Akcha F, Heymann D, Vallette, FM, Mosser J, Ory B, Cartron PF. Cytosine methylation of mature microRNAs inhibits their functions and is associated with poor prognosis in glioblastoma multiforme. Mol Cancer. 2020 Feb 25;19(1):36. doi: 10.1186/s12943-020-01155-z.
• Rabé M, Dumont S, Álvarez-Arenas A, Janati H, Belmonte-Beitia J, Calvo GF, Thibault-Carpentier C, Séry Q, Chauvin C, Joalland N, Briand F, Blandin S, Scotet E, Pecqueur C, Clairambault J, Oliver L, Perez-Garcia V, Nadaradjane A, Cartron PF, Gratas C, Vallette FM. Identification of a transient state during the acquisition of temozolomide resistance in glioblastoma. Cell Death Dis. 2020 Jan 6;11(1):19. 
• Duforestel M, Briand J, Bougras-Cartron G, Heymann D, Frenel JS, Vallette FM, Cartron PF. Cell-free circulating epimarks in cancer monitoring. Epigenomics. 2020 Jan;12(2):145-155. doi: 10.2217/epi-2019-0170. 
• Cartron PF, Cheray M, Bretaudeau L. Epigenetic protein complexes: the adequate candidates for the use of a new generation of epidrugs in personalized and precision medicine in cancer. Epigenomics. 2020 Jan;12(2):171-177. doi: 10.2217/epi-2019-0169.
• Guen VJ, Prigent C. Targeting Primary Ciliogenesis with Small-Molecule Inhibitors. Cell Chem Biol. 2020 Oct 15;27(10):1224-1228. .
• Wilson MM, Weinberg RA, Lees JA, Guen VJ. Emerging Mechanisms by which EMT Programs Control Stemness. Trends Cancer. 2020 Sep;6(9):775-780. 
• Mignard V, Dubois N, Lanoé D, Joalland MP, Oliver L, Pecqueur C, Heymann D, Paris F, Vallette FM, Lalier L. Sphingolipid distribution at mitochondria-associated membranes (MAMs) upon induction of apoptosis. J Lipid Res. 2020 Jul;61(7):1025-1037.

2019

• Louault K, Bonneaud TL, Séveno C, Gomez-Bougie P, Nguyen F, Gautier F, Bourgeois N, Loussouarn D, Kerdraon O, Barillé-Nion S, Jézéquel P, Campone M, Amiot M, Juin PP, Souazé F. Interactions between cancer-associated fibroblasts and tumor cells promote MCL-1 dependency in estrogen receptor-positive breast cancers. Oncogene. 2019 Apr;38(17):3261-3273. doi: 10.1038/s41388-018-0635-z. 
• Avril P, Vidal L, Barille-Nion S, Le Nail LR, Redini F, Layrolle P, Pinault M, Chevalier S, Perrot P, Trichet V. Epinephrine Infiltration of Adipose Tissue Impacts MCF7 Breast Cancer Cells and Total Lipid Content. Int J Mol Sci. 2019 Nov 11;20(22). pii: E5626.
• Ramana Murthy AV, Narendar V, Kumar NS, Aparna P, Durga Bhavani AK, Gautier F, Barillé-Nion S, Juin P, Mosset P, Grée R, Levoin N. Targeting PUMA/Bcl-xL interaction by new specific compounds to unleash apoptotic process in cancer cells. Eur J Med Chem. 2019 Jan 15;162:334-347.
• Briand J, Nadaradjane A, Bougras-Cartron G, Olivier C, Vallette FM, Cartron PF. Diuron exposure and Akt overexpression promote glioma formation through DNA hypomethylation. Clin Epigenetics. 2019 Nov 14;11(1):159. doi: 10.1186/s13148-019-0759-1. 
• Duforestel M, Nadaradjane A, Bougras-Cartron G, Briand J, Olivier C, Frenel JS, Vallette FM, Lelièvre SA, Cartron PF. Glyphosate Primes Mammary Cells for Tumorigenesis by Reprogramming the Epigenome in a TET3-Dependent Manner. Front Genet. 2019 Sep 27;10:885. doi: 10.3389/fgene.2019.00885. 
• Vallette FM, Olivier C, Lézot F, Oliver L, Cochonneau D, Lalier L, Cartron PF, Heymann D. Dormant, quiescent, tolerant and persister cells: Four synonyms for the same target in cancer. Biochem Pharmacol. 2019 Apr;162:169-176. doi: 10.1016/j.bcp.2018.11.004.
• Brown HK, Tellez-Gabriel M, Cartron PF, Vallette FM, Heymann MF, Heymann D. Characterization of circulating tumor cells as a reflection of the tumor heterogeneity: myth or reality? Drug Discov Today. 2019 Mar;24(3):763-772. doi: 10.1016/j.drudis.2018.11.017.
• Blanquart C, Linot C, Cartron PF, Tomaselli D, Mai A, Bertrand P. Epigenetic Metalloenzymes. Curr Med Chem. 2019;26(15):2748-2785. 

2018

• Aira L., Villa E., Colosetti P., Gamas P., Signetti L., Obba S., Proics E., Gautier F., Bailly-Maitre B., Jacquel A., Robert G., Luciano F., Juin P., Ricci J.-E., Auberger P., Marchetti S. The oncogenic tyrosine kinase Lyn impairs the pro-apoptotic function of Bim. Oncogene, (2018) 37(16):2122-2136. 
• Jézéquel P., Campone M. Comment on “How the evolution of multicellularity set the stage for cancer”. British Journal of Cancer (2018) Réf. HAL: inserm-01823385 
• Anne Lok, Géraldine Descamps, Benoit Tessoulin, David Chiron, Marion Eveillard, Catherine Godon, Yannick Le Bris, Astrid Vabret, Céline Bellanger, Laurent Maillet, Sophie Barillé-Nion, Marc Gregoire, Jean-François Fonteneau, Steven Le Gouill, Philippe Moreau, Frederic Tangy, Martine Amiot, Agnès Moreau-Aubry, Catherine Pellat-Deceunynck. p53 regulates CD46 expression and measles virus infection in myeloma cells. Blood Advances (2018) 23(2) :3492 Réf. HAL : inserm-01957487 
• Allègre J., Cartier J., Glorian V., Nathalie D., Dumetier B., Kayaci C., Berthelet J., Gemble S., Vuillier C., Maillet L., Garrido C., Dubrez L. E2F1 binds to the peptide-binding groove within the BIR3 domain of cIAP1 and requires cIAP1 for chromatin binding. PLoS ONE, (2018) 13(10):e0206253.  Réf. HAL: hal-01923499
• Galluzzi L, et al. Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018. Cell Death and Differentiation, (2018) 25(3):486-541. 
• Hedir S, De Giorgi M, Fogha J, De Pascale M, Weiswald LB, Brotin E, Marekha B, Denoyelle C, Denis C, Suzanne P, Gautier F, Juin P, Ligat L, Lopez F, Carlier L, Legay R, Bureau R, Rault S, Poulain L, Oliveira Santos JS, Voisin-Chiret AS. Structure-guided design of pyridoclax derivatives based on Noxa / Mcl-1 interaction mode. Eur J Med Chem. 2018 Nov 5;159:357-380.
• Nadaradjane A, Briand J, Bougras-Cartron G, Disdero V, Vallette FM, Frenel JS, Cartron PF. miR-370-3p Is a Therapeutic Tool in Anti-glioblastoma Therapy but Is Not an Intratumoral or Cell-free Circulating Biomarker. Mol Ther Nucleic Acids. 2018 Dec 7;13:642-650. doi: 10.1016/j.omtn.2018.09.007. 
• Georges S, Calleja LR, Jacques C, Lavaud M, Moukengue B, Lecanda F, Quillard T, Gabriel MT, Cartron PF, Baud'huin M, Lamoureux F, Heymann D, Ory B. Loss of miR-198 and -206 during primary tumor progression enables metastatic dissemination in human osteosarcoma. Oncotarget. 2018 Nov 6;9(87):35726-35741.
• Hervouet E, Peixoto P, Delage-Mourroux R, Boyer-Guittaut M, Cartron PF. Specific or not specific recruitment of DNMTs for DNA methylation, an epigenetic dilemma. Clin Epigenetics. 2018 Feb 9;10:17. doi: 10.1186/s13148-018-0450-y. 
• Asgarova A, Asgarov K, Godet Y, Peixoto P, Nadaradjane A, Boyer-Guittaut M, Galaine J, Guenat D, Mougey V, Perrard J, Pallandre JR, Bouard A, Balland J, Tirole C, Adotevi O, Hendrick E, Herfs M, Cartron PF, Borg C, Hervouet E. PD-L1 expression is regulated by both DNA methylation and NF-kB during EMT signaling in non-small cell lung carcinoma. Oncoimmunology. 2018 Feb 1;7(5):e1423170. 

2017

 

• Carné Trécesson S, Souazé F, Basseville A, Bernard AC, Pécot J, Lopez J, Bessou M, Sarosiek KA, Letai A, Barillé-Nion S, Valo I, Coqueret O, Guette C, Campone M, Gautier F, Juin PP. BCL-XL directly modulates RAS signalling to favour cancer cell stemness. Nat Commun. 2017 Oct 24;8(1):1123. doi: 10.1038/s41467-017-01079-1.
• Céline Vuillier, Steven Lohard, Aurélie Fétiveau, Jennifer Allègre, Cémile Kayaci, Louise E King, Frédérique Braun, Sophie Barillé-Nion, Fabien Gautier, Laurence Dubrez, Andrew P Gilmore, Philippe P Juin, Laurent Maillet. E2F1 interacts with BCL-xL and regulates its subcellular localization dynamics to trigger cell death. Embo Reports First published: 12 December 2017. DOI: 10.15252/embr.201744046 
• Mathot P, Grandin M, Devailly G, Souaze F, Cahais V, Moran S, Campone M, Herceg Z, Esteller M, Juin P, Mehlen P, Dante R. DNA methylation signal has a major role in the response of human breast cancer cells to the microenvironment. Oncogenesis. 2017 Oct 23;6(10):e390. doi: 10.1038/oncsis.2017.88.
• Tea I, Martineau E, Antheaume I, Lalande J, Mauve C, Gilard F, Barillé-Nion S, Blackburn AC, Tcherkez G. 13C and 15N natural isotope abundance reflects breast cancer cell metabolism. Sci Rep. 2016 Sep 28;6:34251. doi: 10.1038/srep34251.
• Chiche A, Moumen M, Romagnoli M, Petit V, Lasla H, Jézéquel P, de la Grange P, Jonkers J, Deugnier MA, Glukhova MA, Faraldo MM. p53 deficiency induces cancer stem cell pool expansion in a mouse model of triple-negative breast tumors. Oncogene. 2017 Apr 27;36(17):2355-2365.
• Olivier Tasseau, Paul Mosset, Sophie Barillé-Nion, Fabien Gautier, Philippe Juin, Nicolas Levoin, Niharika Amireddy, Shasi Kalivendi, René Grée. Synthesis and cytotoxicity studies of new designed benzyl-hydroquinone derivatives. Medicinal Chemistry Research. Accepted
• Bagacean C, Tempescul A, Le Dantec C, Bordron A, Mohr A, Saad H, Olivier V,
• Zdrenghea M, Cristea V, Cartron PF, Douet-Guilbert N, Berthou C, Renaudineau Y. Alterations in DNA methylation/demethylation intermediates predict clinical outcome in chronic lymphocytic leukemia. Oncotarget. 2017 Aug 9;8(39):65699-65716. 
• Guen VJ, Chavarria TE, Kröger C, Ye X, Weinberg RA, Lees JA. EMT programs promote basal mammary stem cell and tumor-initiating cell stemness by inducing primary ciliogenesis and Hedgehog signaling. Proc Natl Acad Sci U S A. 2017 Dec 5;114(49):E10532-E10539. 
• Guen VJ, Gamble C, Lees JA, Colas P. The awakening of the CDK10/Cyclin M protein kinase. Oncotarget. 2017 Jul 25;8(30):50174-50186. 
• Raimbourg J, Joalland MP, Cabart M, de Plater L, Bouquet F, Savina A, Decaudin D, Bennouna J, Vallette FM, Lalier L. Sensitization of EGFR Wild-Type Non-Small Cell Lung Cancer Cells to EGFR-Tyrosine Kinase Inhibitor Erlotinib. Mol Cancer Ther. 2017 Aug;16(8):1634-1644.

If like us, you are interested in understanding cancers and imagining tomorrow’s personalized medicine in oncology, do not hesitate to contact us.

Master 2

Etude des mécanismes cellulaires sous-jacents à la résistance aux traitements des cancers du sein induites par les fibroblastes du microenvironnement tumoral.
Contact : frederique.souaze@univ-nantes.fr.

PhD Thesis

No specific announcement at the moment. 

Post docs

No specific announcement at the moment.

Others job opportunities

No specific announcement at the moment.
However, if you are interested in joining the team, please feel free to submit your spontaneous applications to philippe.juin@inserm.fr 

One team - Two laboratory sites

IRS-UN  Nantes (quai Moncousu) ICO Site Saint Herblain (boulevard Jacques Monod)