A stemness-related ZEB1-MSRB3 axis governs cellular pliancy and breast cancer genome stability.
Identifieur interne : 001260 ( Main/Exploration ); précédent : 001259; suivant : 001261A stemness-related ZEB1-MSRB3 axis governs cellular pliancy and breast cancer genome stability.
Auteurs : Anne-Pierre Morel [France] ; Christophe Ginestier [France] ; Roxane M. Pommier [France] ; Olivier Cabaud [France] ; Emmanuelle Ruiz [France] ; Julien Wicinski [France] ; Mojgan Devouassoux-Shisheboran [France] ; Valérie Combaret [France] ; Pascal Finetti [France] ; Christelle Chassot [France] ; Christiane Pinatel [France] ; Frédérique Fauvet [France] ; Pierre Saintigny [France] ; Emilie Thomas [France] ; Caroline Moyret-Lalle [France] ; Joël Lachuer [France] ; Emmanuelle Despras [France] ; Jean-Luc Jauffret [France] ; François Bertucci [France] ; Jérôme Guitton [France] ; Anne Wierinckx [France] ; Qing Wang [France] ; Nina Radosevic-Robin [France] ; Frédérique Penault-Llorca [France] ; David G. Cox [France] ; Frédéric Hollande [Australie] ; Stéphane Ansieau [France] ; Julie Caramel [France] ; Daniel Birnbaum [France] ; Arnaud M. Vigneron [France] ; Agnès Tissier [France] ; Emmanuelle Charafe-Jauffret [France] ; Alain Puisieux [France]Source :
- Nature medicine [ 1546-170X ] ; 2017.
Descripteurs français
- KwdFr :
- Adolescent, Adulte, Adulte d'âge moyen, Altération de l'ADN, Analyse de profil d'expression de gènes, Analyse de séquence d'ADN, Analyse sur puce à tissus, Animaux, Carcinomes (génétique), Carcinomes (métabolisme), Cellules souches (cytologie), Cellules souches (métabolisme), Cellules épithéliales (cytologie), Cellules épithéliales (métabolisme), Cytométrie en flux, Différenciation cellulaire (génétique), Espèces réactives de l'oxygène, Facteur de transcription Zeb1 (génétique), Facteur de transcription Zeb1 (métabolisme), Femelle, Glandes mammaires humaines (cytologie), Humains, Immunoprécipitation de la chromatine, Immunotransfert, Instabilité du génome (génétique), Jeune adulte, Lignée cellulaire tumorale, Methionine Sulfoxide Reductases (génétique), Methionine Sulfoxide Reductases (métabolisme), Protéine p53 suppresseur de tumeur (génétique), Protéine p53 suppresseur de tumeur (métabolisme), Réaction de polymérisation en chaine en temps réel, Régulation de l'expression des gènes tumoraux, Souris de lignée NOD, Sujet âgé, Sujet âgé de 80 ans ou plus, Technique d'immunofluorescence, Transformation cellulaire néoplasique (génétique), Tumeurs du sein (génétique), Tumeurs du sein (métabolisme).
- MESH :
- cytologie : Cellules souches, Cellules épithéliales, Glandes mammaires humaines.
- génétique : Carcinomes, Différenciation cellulaire, Facteur de transcription Zeb1, Instabilité du génome, Methionine Sulfoxide Reductases, Protéine p53 suppresseur de tumeur, Transformation cellulaire néoplasique, Tumeurs du sein.
- métabolisme : Carcinomes, Cellules souches, Cellules épithéliales, Facteur de transcription Zeb1, Methionine Sulfoxide Reductases, Protéine p53 suppresseur de tumeur, Tumeurs du sein.
- Adolescent, Adulte, Adulte d'âge moyen, Altération de l'ADN, Analyse de profil d'expression de gènes, Analyse de séquence d'ADN, Analyse sur puce à tissus, Animaux, Cytométrie en flux, Espèces réactives de l'oxygène, Femelle, Humains, Immunoprécipitation de la chromatine, Immunotransfert, Jeune adulte, Lignée cellulaire tumorale, Réaction de polymérisation en chaine en temps réel, Régulation de l'expression des gènes tumoraux, Souris de lignée NOD, Sujet âgé, Sujet âgé de 80 ans ou plus, Technique d'immunofluorescence.
English descriptors
- KwdEn :
- Adolescent, Adult, Aged, Aged, 80 and over, Animals, Breast Neoplasms (genetics), Breast Neoplasms (metabolism), Carcinoma (genetics), Carcinoma (metabolism), Cell Differentiation (genetics), Cell Line, Tumor, Cell Transformation, Neoplastic (genetics), Chromatin Immunoprecipitation, DNA Damage, Epithelial Cells (cytology), Epithelial Cells (metabolism), Female, Flow Cytometry, Fluorescent Antibody Technique, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Genomic Instability (genetics), Humans, Immunoblotting, Mammary Glands, Human (cytology), Methionine Sulfoxide Reductases (genetics), Methionine Sulfoxide Reductases (metabolism), Mice, Inbred NOD, Middle Aged, Reactive Oxygen Species, Real-Time Polymerase Chain Reaction, Sequence Analysis, DNA, Stem Cells (cytology), Stem Cells (metabolism), Tissue Array Analysis, Tumor Suppressor Protein p53 (genetics), Tumor Suppressor Protein p53 (metabolism), Young Adult, Zinc Finger E-box-Binding Homeobox 1 (genetics), Zinc Finger E-box-Binding Homeobox 1 (metabolism).
- MESH :
- chemical , genetics : Methionine Sulfoxide Reductases, Tumor Suppressor Protein p53, Zinc Finger E-box-Binding Homeobox 1.
- cytology : Epithelial Cells, Mammary Glands, Human, Stem Cells.
- genetics : Breast Neoplasms, Carcinoma, Cell Differentiation, Cell Transformation, Neoplastic, Genomic Instability.
- metabolism : Breast Neoplasms, Carcinoma, Epithelial Cells, Methionine Sulfoxide Reductases, Stem Cells, Tumor Suppressor Protein p53, Zinc Finger E-box-Binding Homeobox 1.
- Adolescent, Adult, Aged, Aged, 80 and over, Animals, Cell Line, Tumor, Chromatin Immunoprecipitation, DNA Damage, Female, Flow Cytometry, Fluorescent Antibody Technique, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Humans, Immunoblotting, Mice, Inbred NOD, Middle Aged, Reactive Oxygen Species, Real-Time Polymerase Chain Reaction, Sequence Analysis, DNA, Tissue Array Analysis, Young Adult.
Abstract
Chromosomal instability (CIN), a feature of most adult neoplasms from their early stages onward, is a driver of tumorigenesis. However, several malignancy subtypes, including some triple-negative breast cancers, display a paucity of genomic aberrations, thus suggesting that tumor development may occur in the absence of CIN. Here we show that the differentiation status of normal human mammary epithelial cells dictates cell behavior after an oncogenic event and predetermines the genetic routes toward malignancy. Whereas oncogene induction in differentiated cells induces massive DNA damage, mammary stem cells are resistant, owing to a preemptive program driven by the transcription factor ZEB1 and the methionine sulfoxide reductase MSRB3. The prevention of oncogene-induced DNA damage precludes induction of the oncosuppressive p53-dependent DNA-damage response, thereby increasing stem cells' intrinsic susceptibility to malignant transformation. In accord with this model, a subclass of breast neoplasms exhibit unique pathological features, including high ZEB1 expression, a low frequency of TP53 mutations and low CIN.
DOI: 10.1038/nm.4323
PubMed: 28394329
Affiliations:
- Australie, France
- Auvergne (région administrative), Auvergne-Rhône-Alpes, Provence-Alpes-Côte d'Azur, Rhône-Alpes, Victoria (État), Île-de-France
- Clermont-Ferrand, Lyon, Marseille, Melbourne, Orsay
- Université Paris-Sud, Université de Melbourne
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Le document en format XML
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xml:lang="fr">France</country><wicri:regionArea>Université Aix Marseille, CNRS, INSERM, Institut Paoli-Calmettes, CRCM, Molecular Oncology, Equipe labellisée Ligue Contre le Cancer, Marseille</wicri:regionArea><placeName><region type="region">Provence-Alpes-Côte d'Azur</region><region type="old region">Provence-Alpes-Côte d'Azur</region><settlement type="city">Marseille</settlement></placeName></affiliation></author><author><name sortKey="Chassot, Christelle" sort="Chassot, Christelle" uniqKey="Chassot C" first="Christelle" last="Chassot">Christelle Chassot</name><affiliation wicri:level="3"><nlm:affiliation>Université de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Cancer Research Center of Lyon, Equipe Labellisée Ligue contre le Cancer, Lyon, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Université de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Cancer Research Center of 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region">Rhône-Alpes</region><settlement type="city">Lyon</settlement></placeName></affiliation></author><author><name sortKey="Fauvet, Frederique" sort="Fauvet, Frederique" uniqKey="Fauvet F" first="Frédérique" last="Fauvet">Frédérique Fauvet</name><affiliation wicri:level="3"><nlm:affiliation>Université de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Cancer Research Center of Lyon, Equipe Labellisée Ligue contre le Cancer, Lyon, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Université de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Cancer Research Center of Lyon, Equipe Labellisée Ligue contre le Cancer, Lyon</wicri:regionArea><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Lyon</settlement></placeName></affiliation></author><author><name sortKey="Saintigny, Pierre" sort="Saintigny, Pierre" uniqKey="Saintigny P" first="Pierre" last="Saintigny">Pierre Saintigny</name><affiliation wicri:level="3"><nlm:affiliation>Université de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Cancer Research Center of Lyon, Equipe Labellisée Ligue contre le Cancer, Lyon, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Université de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Cancer Research Center of Lyon, Equipe Labellisée Ligue contre le Cancer, Lyon</wicri:regionArea><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Lyon</settlement></placeName></affiliation></author><author><name sortKey="Thomas, Emilie" sort="Thomas, Emilie" uniqKey="Thomas E" first="Emilie" last="Thomas">Emilie Thomas</name><affiliation wicri:level="3"><nlm:affiliation>Fondation Synergie Lyon Cancer, Centre Léon Bérard, Lyon, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Fondation Synergie Lyon Cancer, Centre Léon Bérard, Lyon</wicri:regionArea><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Lyon</settlement></placeName></affiliation></author><author><name sortKey="Moyret Lalle, Caroline" sort="Moyret Lalle, Caroline" uniqKey="Moyret Lalle C" first="Caroline" last="Moyret-Lalle">Caroline Moyret-Lalle</name><affiliation wicri:level="3"><nlm:affiliation>Université de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Cancer Research Center of Lyon, Equipe Labellisée Ligue contre le Cancer, Lyon, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Université de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Cancer Research Center of Lyon, Equipe Labellisée Ligue contre le Cancer, Lyon</wicri:regionArea><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Lyon</settlement></placeName></affiliation></author><author><name sortKey="Lachuer, Joel" sort="Lachuer, Joel" uniqKey="Lachuer J" first="Joël" last="Lachuer">Joël Lachuer</name><affiliation wicri:level="3"><nlm:affiliation>Université de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Cancer Research Center of Lyon, Equipe Labellisée Ligue contre le Cancer, Lyon, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Université de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Cancer Research Center of Lyon, Equipe Labellisée Ligue contre le Cancer, Lyon</wicri:regionArea><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Lyon</settlement></placeName></affiliation></author><author><name sortKey="Despras, Emmanuelle" sort="Despras, Emmanuelle" uniqKey="Despras E" first="Emmanuelle" last="Despras">Emmanuelle Despras</name><affiliation wicri:level="4"><nlm:affiliation>Université Paris-Sud, CNRS-UMR 8200, Unit of Genetic Stability and Oncogenesis, Equipe Labellisée Ligue contre le Cancer, Institut de Cancérologie Gustave Roussy, Villejuif, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Université Paris-Sud, CNRS-UMR 8200, Unit of Genetic Stability and Oncogenesis, Equipe Labellisée Ligue contre le Cancer, Institut de Cancérologie Gustave Roussy, Villejuif</wicri:regionArea><wicri:noRegion>Villejuif</wicri:noRegion><orgName type="university">Université Paris-Sud</orgName><placeName><settlement type="city">Orsay</settlement><region type="region" nuts="2">Île-de-France</region></placeName></affiliation></author><author><name sortKey="Jauffret, Jean Luc" sort="Jauffret, Jean Luc" uniqKey="Jauffret J" first="Jean-Luc" last="Jauffret">Jean-Luc Jauffret</name><affiliation wicri:level="3"><nlm:affiliation>Clinique Phenicia, Marseille, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Clinique Phenicia, Marseille</wicri:regionArea><placeName><region type="region">Provence-Alpes-Côte d'Azur</region><region type="old region">Provence-Alpes-Côte d'Azur</region><settlement type="city">Marseille</settlement></placeName></affiliation></author><author><name sortKey="Bertucci, Francois" sort="Bertucci, Francois" uniqKey="Bertucci F" first="François" last="Bertucci">François Bertucci</name><affiliation wicri:level="3"><nlm:affiliation>Université Aix Marseille, CNRS, INSERM, Institut Paoli-Calmettes, CRCM, Molecular Oncology, Equipe labellisée Ligue Contre le Cancer, Marseille, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Université Aix Marseille, CNRS, INSERM, Institut Paoli-Calmettes, CRCM, Molecular Oncology, Equipe labellisée Ligue Contre le Cancer, Marseille</wicri:regionArea><placeName><region type="region">Provence-Alpes-Côte d'Azur</region><region type="old region">Provence-Alpes-Côte d'Azur</region><settlement type="city">Marseille</settlement></placeName></affiliation></author><author><name sortKey="Guitton, Jerome" sort="Guitton, Jerome" uniqKey="Guitton J" first="Jérôme" last="Guitton">Jérôme Guitton</name><affiliation wicri:level="1"><nlm:affiliation>Université de Lyon, Université Claude Bernard Lyon 1, Hospices Civils de Lyon, Centre Hospitalier Lyon-Sud, Pierre Bénite, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Université de Lyon, Université Claude Bernard Lyon 1, Hospices Civils de Lyon, Centre Hospitalier Lyon-Sud, Pierre Bénite</wicri:regionArea><wicri:noRegion>Pierre Bénite</wicri:noRegion><wicri:noRegion>Pierre Bénite</wicri:noRegion></affiliation></author><author><name sortKey="Wierinckx, Anne" sort="Wierinckx, Anne" uniqKey="Wierinckx A" first="Anne" last="Wierinckx">Anne Wierinckx</name><affiliation wicri:level="3"><nlm:affiliation>Université de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Cancer Research Center of Lyon, Equipe Labellisée Ligue contre le Cancer, Lyon, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Université de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Cancer Research Center of Lyon, Equipe Labellisée Ligue contre le Cancer, Lyon</wicri:regionArea><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Lyon</settlement></placeName></affiliation></author><author><name sortKey="Wang, Qing" sort="Wang, Qing" uniqKey="Wang Q" first="Qing" last="Wang">Qing Wang</name><affiliation wicri:level="3"><nlm:affiliation>Centre Léon Bérard, Lyon, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Centre Léon Bérard, Lyon</wicri:regionArea><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Lyon</settlement></placeName></affiliation></author><author><name sortKey="Radosevic Robin, Nina" sort="Radosevic Robin, Nina" uniqKey="Radosevic Robin N" first="Nina" last="Radosevic-Robin">Nina Radosevic-Robin</name><affiliation wicri:level="3"><nlm:affiliation>Department of Pathology, Jean Perrin Cancer Center and ERTICa Research Group, University of Auvergne, Clermont-Ferrand, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Department of Pathology, Jean Perrin Cancer Center and ERTICa Research Group, University of Auvergne, Clermont-Ferrand</wicri:regionArea><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Auvergne (région administrative)</region><settlement type="city">Clermont-Ferrand</settlement></placeName></affiliation></author><author><name sortKey="Penault Llorca, Frederique" sort="Penault Llorca, Frederique" uniqKey="Penault Llorca F" first="Frédérique" last="Penault-Llorca">Frédérique Penault-Llorca</name><affiliation wicri:level="3"><nlm:affiliation>Department of Pathology, Jean Perrin Cancer Center and ERTICa Research Group, University of Auvergne, Clermont-Ferrand, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Department of Pathology, Jean Perrin Cancer Center and ERTICa Research Group, University of Auvergne, Clermont-Ferrand</wicri:regionArea><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Auvergne (région administrative)</region><settlement type="city">Clermont-Ferrand</settlement></placeName></affiliation></author><author><name sortKey="Cox, David G" sort="Cox, David G" uniqKey="Cox D" first="David G" last="Cox">David G. Cox</name><affiliation wicri:level="3"><nlm:affiliation>Université de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Cancer Research Center of Lyon, Equipe Labellisée Ligue contre le Cancer, Lyon, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Université de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Cancer Research Center of Lyon, Equipe Labellisée Ligue contre le Cancer, Lyon</wicri:regionArea><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Lyon</settlement></placeName></affiliation></author><author><name sortKey="Hollande, Frederic" sort="Hollande, Frederic" uniqKey="Hollande F" first="Frédéric" last="Hollande">Frédéric Hollande</name><affiliation wicri:level="4"><nlm:affiliation>Department of Pathology, University of Melbourne, Parkville, Victoria, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Pathology, University of Melbourne, Parkville, Victoria</wicri:regionArea><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Ansieau, Stephane" sort="Ansieau, Stephane" uniqKey="Ansieau S" first="Stéphane" last="Ansieau">Stéphane Ansieau</name><affiliation wicri:level="3"><nlm:affiliation>Université de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Cancer Research Center of Lyon, Equipe Labellisée Ligue contre le Cancer, Lyon, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Université de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Cancer Research Center of Lyon, Equipe Labellisée Ligue contre le Cancer, Lyon</wicri:regionArea><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Lyon</settlement></placeName></affiliation></author><author><name sortKey="Caramel, Julie" sort="Caramel, Julie" uniqKey="Caramel J" first="Julie" last="Caramel">Julie Caramel</name><affiliation wicri:level="3"><nlm:affiliation>Université de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Cancer Research Center of Lyon, Equipe Labellisée Ligue contre le Cancer, Lyon, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Université de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Cancer Research Center of Lyon, Equipe Labellisée Ligue contre le Cancer, Lyon</wicri:regionArea><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Lyon</settlement></placeName></affiliation></author><author><name sortKey="Birnbaum, Daniel" sort="Birnbaum, Daniel" uniqKey="Birnbaum D" first="Daniel" last="Birnbaum">Daniel Birnbaum</name><affiliation wicri:level="3"><nlm:affiliation>Université Aix Marseille, CNRS, INSERM, Institut Paoli-Calmettes, CRCM, Molecular Oncology, Equipe labellisée Ligue Contre le Cancer, Marseille, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Université Aix Marseille, CNRS, INSERM, Institut Paoli-Calmettes, CRCM, Molecular Oncology, Equipe labellisée Ligue Contre le Cancer, Marseille</wicri:regionArea><placeName><region type="region">Provence-Alpes-Côte d'Azur</region><region type="old region">Provence-Alpes-Côte d'Azur</region><settlement type="city">Marseille</settlement></placeName></affiliation></author><author><name sortKey="Vigneron, Arnaud M" sort="Vigneron, Arnaud M" uniqKey="Vigneron A" first="Arnaud M" last="Vigneron">Arnaud M. Vigneron</name><affiliation wicri:level="3"><nlm:affiliation>Université de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Cancer Research Center of Lyon, Equipe Labellisée Ligue contre le Cancer, Lyon, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Université de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Cancer Research Center of Lyon, Equipe Labellisée Ligue contre le Cancer, Lyon</wicri:regionArea><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Lyon</settlement></placeName></affiliation></author><author><name sortKey="Tissier, Agnes" sort="Tissier, Agnes" uniqKey="Tissier A" first="Agnès" last="Tissier">Agnès Tissier</name><affiliation wicri:level="3"><nlm:affiliation>Université de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Cancer Research Center of Lyon, Equipe Labellisée Ligue contre le Cancer, Lyon, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Université de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Cancer Research Center of Lyon, Equipe Labellisée Ligue contre le Cancer, Lyon</wicri:regionArea><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Lyon</settlement></placeName></affiliation></author><author><name sortKey="Charafe Jauffret, Emmanuelle" sort="Charafe Jauffret, Emmanuelle" uniqKey="Charafe Jauffret E" first="Emmanuelle" last="Charafe-Jauffret">Emmanuelle Charafe-Jauffret</name><affiliation wicri:level="3"><nlm:affiliation>Université Aix Marseille, CNRS, INSERM, Institut Paoli-Calmettes, CRCM, Molecular Oncology, Equipe labellisée Ligue Contre le Cancer, Marseille, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Université Aix Marseille, CNRS, INSERM, Institut Paoli-Calmettes, CRCM, Molecular Oncology, Equipe labellisée Ligue Contre le Cancer, Marseille</wicri:regionArea><placeName><region type="region">Provence-Alpes-Côte d'Azur</region><region type="old region">Provence-Alpes-Côte d'Azur</region><settlement type="city">Marseille</settlement></placeName></affiliation></author><author><name sortKey="Puisieux, Alain" sort="Puisieux, Alain" uniqKey="Puisieux A" first="Alain" last="Puisieux">Alain Puisieux</name><affiliation wicri:level="3"><nlm:affiliation>Université de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Cancer Research Center of Lyon, Equipe Labellisée Ligue contre le Cancer, Lyon, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Université de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Cancer Research Center of Lyon, Equipe Labellisée Ligue contre le Cancer, Lyon</wicri:regionArea><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Lyon</settlement></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2017">2017</date><idno type="RBID">pubmed:28394329</idno><idno type="pmid">28394329</idno><idno type="doi">10.1038/nm.4323</idno><idno type="wicri:Area/PubMed/Corpus">000C25</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000C25</idno><idno type="wicri:Area/PubMed/Curation">000C22</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000C22</idno><idno type="wicri:Area/PubMed/Checkpoint">000C22</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">000C22</idno><idno type="wicri:Area/Ncbi/Merge">004617</idno><idno type="wicri:Area/Ncbi/Curation">004617</idno><idno type="wicri:Area/Ncbi/Checkpoint">004617</idno><idno type="wicri:Area/Main/Merge">001255</idno><idno type="wicri:Area/Main/Curation">001260</idno><idno type="wicri:Area/Main/Exploration">001260</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">A stemness-related ZEB1-MSRB3 axis governs cellular pliancy and breast cancer genome stability.</title><author><name sortKey="Morel, Anne Pierre" sort="Morel, Anne Pierre" uniqKey="Morel A" first="Anne-Pierre" last="Morel">Anne-Pierre Morel</name><affiliation wicri:level="3"><nlm:affiliation>Université de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Cancer Research Center of Lyon, Equipe Labellisée Ligue contre le Cancer, Lyon, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Université de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Cancer Research Center of Lyon, Equipe Labellisée Ligue contre le Cancer, Lyon</wicri:regionArea><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Lyon</settlement></placeName></affiliation></author><author><name sortKey="Ginestier, Christophe" sort="Ginestier, Christophe" uniqKey="Ginestier C" first="Christophe" last="Ginestier">Christophe Ginestier</name><affiliation wicri:level="3"><nlm:affiliation>Université Aix Marseille, CNRS, INSERM, Institut Paoli-Calmettes, CRCM, Molecular Oncology, Equipe labellisée Ligue Contre le Cancer, Marseille, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Université Aix Marseille, CNRS, INSERM, Institut Paoli-Calmettes, CRCM, Molecular Oncology, Equipe labellisée Ligue Contre le Cancer, Marseille</wicri:regionArea><placeName><region type="region">Provence-Alpes-Côte d'Azur</region><region type="old region">Provence-Alpes-Côte d'Azur</region><settlement type="city">Marseille</settlement></placeName></affiliation></author><author><name sortKey="Pommier, Roxane M" sort="Pommier, Roxane M" uniqKey="Pommier R" first="Roxane M" last="Pommier">Roxane M. Pommier</name><affiliation wicri:level="3"><nlm:affiliation>Université de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Cancer Research Center of Lyon, Equipe Labellisée Ligue contre le Cancer, Lyon, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Université de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Cancer Research Center of Lyon, Equipe Labellisée Ligue contre le Cancer, Lyon</wicri:regionArea><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Lyon</settlement></placeName></affiliation></author><author><name sortKey="Cabaud, Olivier" sort="Cabaud, Olivier" uniqKey="Cabaud O" first="Olivier" last="Cabaud">Olivier Cabaud</name><affiliation wicri:level="3"><nlm:affiliation>Université Aix Marseille, CNRS, INSERM, Institut Paoli-Calmettes, CRCM, Molecular Oncology, Equipe labellisée Ligue Contre le Cancer, Marseille, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Université Aix Marseille, CNRS, INSERM, Institut Paoli-Calmettes, CRCM, Molecular Oncology, Equipe labellisée Ligue Contre le Cancer, Marseille</wicri:regionArea><placeName><region type="region">Provence-Alpes-Côte d'Azur</region><region type="old region">Provence-Alpes-Côte d'Azur</region><settlement type="city">Marseille</settlement></placeName></affiliation></author><author><name sortKey="Ruiz, Emmanuelle" sort="Ruiz, Emmanuelle" uniqKey="Ruiz E" first="Emmanuelle" last="Ruiz">Emmanuelle Ruiz</name><affiliation wicri:level="3"><nlm:affiliation>Université de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Cancer Research Center of Lyon, Equipe Labellisée Ligue contre le Cancer, Lyon, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Université de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Cancer Research Center of Lyon, Equipe Labellisée Ligue contre le Cancer, Lyon</wicri:regionArea><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Lyon</settlement></placeName></affiliation></author><author><name sortKey="Wicinski, Julien" sort="Wicinski, Julien" uniqKey="Wicinski J" first="Julien" last="Wicinski">Julien Wicinski</name><affiliation wicri:level="3"><nlm:affiliation>Université Aix Marseille, CNRS, INSERM, Institut Paoli-Calmettes, CRCM, Molecular Oncology, Equipe labellisée Ligue Contre le Cancer, Marseille, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Université Aix Marseille, CNRS, INSERM, Institut Paoli-Calmettes, CRCM, Molecular Oncology, Equipe labellisée Ligue Contre le Cancer, Marseille</wicri:regionArea><placeName><region type="region">Provence-Alpes-Côte d'Azur</region><region type="old region">Provence-Alpes-Côte d'Azur</region><settlement type="city">Marseille</settlement></placeName></affiliation></author><author><name sortKey="Devouassoux Shisheboran, Mojgan" sort="Devouassoux Shisheboran, Mojgan" uniqKey="Devouassoux Shisheboran M" first="Mojgan" last="Devouassoux-Shisheboran">Mojgan Devouassoux-Shisheboran</name><affiliation wicri:level="3"><nlm:affiliation>Université de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Cancer Research Center of Lyon, Equipe Labellisée Ligue contre le Cancer, Lyon, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Université de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Cancer Research Center of Lyon, Equipe Labellisée Ligue contre le Cancer, Lyon</wicri:regionArea><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Lyon</settlement></placeName></affiliation></author><author><name sortKey="Combaret, Valerie" sort="Combaret, Valerie" uniqKey="Combaret V" first="Valérie" last="Combaret">Valérie Combaret</name><affiliation wicri:level="3"><nlm:affiliation>Centre Léon Bérard, Lyon, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Centre Léon Bérard, Lyon</wicri:regionArea><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Lyon</settlement></placeName></affiliation></author><author><name sortKey="Finetti, Pascal" sort="Finetti, Pascal" uniqKey="Finetti P" first="Pascal" last="Finetti">Pascal Finetti</name><affiliation wicri:level="3"><nlm:affiliation>Université Aix Marseille, CNRS, INSERM, Institut Paoli-Calmettes, CRCM, Molecular Oncology, Equipe labellisée Ligue Contre le Cancer, Marseille, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Université Aix Marseille, CNRS, INSERM, Institut Paoli-Calmettes, CRCM, Molecular Oncology, Equipe labellisée Ligue Contre le Cancer, Marseille</wicri:regionArea><placeName><region type="region">Provence-Alpes-Côte d'Azur</region><region type="old region">Provence-Alpes-Côte d'Azur</region><settlement type="city">Marseille</settlement></placeName></affiliation></author><author><name sortKey="Chassot, Christelle" sort="Chassot, Christelle" uniqKey="Chassot C" first="Christelle" last="Chassot">Christelle Chassot</name><affiliation wicri:level="3"><nlm:affiliation>Université de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Cancer Research Center of Lyon, Equipe Labellisée Ligue contre le Cancer, Lyon, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Université de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Cancer Research Center of Lyon, Equipe Labellisée Ligue contre le Cancer, Lyon</wicri:regionArea><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Lyon</settlement></placeName></affiliation></author><author><name sortKey="Pinatel, Christiane" sort="Pinatel, Christiane" uniqKey="Pinatel C" first="Christiane" last="Pinatel">Christiane Pinatel</name><affiliation wicri:level="3"><nlm:affiliation>Université de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Cancer Research Center of Lyon, Equipe Labellisée Ligue contre le Cancer, Lyon, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Université de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Cancer Research Center of Lyon, Equipe Labellisée Ligue contre le Cancer, Lyon</wicri:regionArea><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Lyon</settlement></placeName></affiliation></author><author><name sortKey="Fauvet, Frederique" sort="Fauvet, Frederique" uniqKey="Fauvet F" first="Frédérique" last="Fauvet">Frédérique Fauvet</name><affiliation wicri:level="3"><nlm:affiliation>Université de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Cancer Research Center of Lyon, Equipe Labellisée Ligue contre le Cancer, Lyon, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Université de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Cancer Research Center of Lyon, Equipe Labellisée Ligue contre le Cancer, Lyon</wicri:regionArea><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Lyon</settlement></placeName></affiliation></author><author><name sortKey="Saintigny, Pierre" sort="Saintigny, Pierre" uniqKey="Saintigny P" first="Pierre" last="Saintigny">Pierre Saintigny</name><affiliation wicri:level="3"><nlm:affiliation>Université de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Cancer Research Center of Lyon, Equipe Labellisée Ligue contre le Cancer, Lyon, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Université de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Cancer Research Center of Lyon, Equipe Labellisée Ligue contre le Cancer, Lyon</wicri:regionArea><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Lyon</settlement></placeName></affiliation></author><author><name sortKey="Thomas, Emilie" sort="Thomas, Emilie" uniqKey="Thomas E" first="Emilie" last="Thomas">Emilie Thomas</name><affiliation wicri:level="3"><nlm:affiliation>Fondation Synergie Lyon Cancer, Centre Léon Bérard, Lyon, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Fondation Synergie Lyon Cancer, Centre Léon Bérard, Lyon</wicri:regionArea><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Lyon</settlement></placeName></affiliation></author><author><name sortKey="Moyret Lalle, Caroline" sort="Moyret Lalle, Caroline" uniqKey="Moyret Lalle C" first="Caroline" last="Moyret-Lalle">Caroline Moyret-Lalle</name><affiliation wicri:level="3"><nlm:affiliation>Université de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Cancer Research Center of Lyon, Equipe Labellisée Ligue contre le Cancer, Lyon, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Université de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Cancer Research Center of Lyon, Equipe Labellisée Ligue contre le Cancer, Lyon</wicri:regionArea><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Lyon</settlement></placeName></affiliation></author><author><name sortKey="Lachuer, Joel" sort="Lachuer, Joel" uniqKey="Lachuer J" first="Joël" last="Lachuer">Joël Lachuer</name><affiliation wicri:level="3"><nlm:affiliation>Université de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Cancer Research Center of Lyon, Equipe Labellisée Ligue contre le Cancer, Lyon, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Université de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Cancer Research Center of Lyon, Equipe Labellisée Ligue contre le Cancer, Lyon</wicri:regionArea><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Lyon</settlement></placeName></affiliation></author><author><name sortKey="Despras, Emmanuelle" sort="Despras, Emmanuelle" uniqKey="Despras E" first="Emmanuelle" last="Despras">Emmanuelle Despras</name><affiliation wicri:level="4"><nlm:affiliation>Université Paris-Sud, CNRS-UMR 8200, Unit of Genetic Stability and Oncogenesis, Equipe Labellisée Ligue contre le Cancer, Institut de Cancérologie Gustave Roussy, Villejuif, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Université Paris-Sud, CNRS-UMR 8200, Unit of Genetic Stability and Oncogenesis, Equipe Labellisée Ligue contre le Cancer, Institut de Cancérologie Gustave Roussy, Villejuif</wicri:regionArea><wicri:noRegion>Villejuif</wicri:noRegion><orgName type="university">Université Paris-Sud</orgName><placeName><settlement type="city">Orsay</settlement><region type="region" nuts="2">Île-de-France</region></placeName></affiliation></author><author><name sortKey="Jauffret, Jean Luc" sort="Jauffret, Jean Luc" uniqKey="Jauffret J" first="Jean-Luc" last="Jauffret">Jean-Luc Jauffret</name><affiliation wicri:level="3"><nlm:affiliation>Clinique Phenicia, Marseille, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Clinique Phenicia, Marseille</wicri:regionArea><placeName><region type="region">Provence-Alpes-Côte d'Azur</region><region type="old region">Provence-Alpes-Côte d'Azur</region><settlement type="city">Marseille</settlement></placeName></affiliation></author><author><name sortKey="Bertucci, Francois" sort="Bertucci, Francois" uniqKey="Bertucci F" first="François" last="Bertucci">François Bertucci</name><affiliation wicri:level="3"><nlm:affiliation>Université Aix Marseille, CNRS, INSERM, Institut Paoli-Calmettes, CRCM, Molecular Oncology, Equipe labellisée Ligue Contre le Cancer, Marseille, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Université Aix Marseille, CNRS, INSERM, Institut Paoli-Calmettes, CRCM, Molecular Oncology, Equipe labellisée Ligue Contre le Cancer, Marseille</wicri:regionArea><placeName><region type="region">Provence-Alpes-Côte d'Azur</region><region type="old region">Provence-Alpes-Côte d'Azur</region><settlement type="city">Marseille</settlement></placeName></affiliation></author><author><name sortKey="Guitton, Jerome" sort="Guitton, Jerome" uniqKey="Guitton J" first="Jérôme" last="Guitton">Jérôme Guitton</name><affiliation wicri:level="1"><nlm:affiliation>Université de Lyon, Université Claude Bernard Lyon 1, Hospices Civils de Lyon, Centre Hospitalier Lyon-Sud, Pierre Bénite, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Université de Lyon, Université Claude Bernard Lyon 1, Hospices Civils de Lyon, Centre Hospitalier Lyon-Sud, Pierre Bénite</wicri:regionArea><wicri:noRegion>Pierre Bénite</wicri:noRegion><wicri:noRegion>Pierre Bénite</wicri:noRegion></affiliation></author><author><name sortKey="Wierinckx, Anne" sort="Wierinckx, Anne" uniqKey="Wierinckx A" first="Anne" last="Wierinckx">Anne Wierinckx</name><affiliation wicri:level="3"><nlm:affiliation>Université de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Cancer Research Center of Lyon, Equipe Labellisée Ligue contre le Cancer, Lyon, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Université de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Cancer Research Center of Lyon, Equipe Labellisée Ligue contre le Cancer, Lyon</wicri:regionArea><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Lyon</settlement></placeName></affiliation></author><author><name sortKey="Wang, Qing" sort="Wang, Qing" uniqKey="Wang Q" first="Qing" last="Wang">Qing Wang</name><affiliation wicri:level="3"><nlm:affiliation>Centre Léon Bérard, Lyon, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Centre Léon Bérard, Lyon</wicri:regionArea><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Lyon</settlement></placeName></affiliation></author><author><name sortKey="Radosevic Robin, Nina" sort="Radosevic Robin, Nina" uniqKey="Radosevic Robin N" first="Nina" last="Radosevic-Robin">Nina Radosevic-Robin</name><affiliation wicri:level="3"><nlm:affiliation>Department of Pathology, Jean Perrin Cancer Center and ERTICa Research Group, University of Auvergne, Clermont-Ferrand, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Department of Pathology, Jean Perrin Cancer Center and ERTICa Research Group, University of Auvergne, Clermont-Ferrand</wicri:regionArea><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Auvergne (région administrative)</region><settlement type="city">Clermont-Ferrand</settlement></placeName></affiliation></author><author><name sortKey="Penault Llorca, Frederique" sort="Penault Llorca, Frederique" uniqKey="Penault Llorca F" first="Frédérique" last="Penault-Llorca">Frédérique Penault-Llorca</name><affiliation wicri:level="3"><nlm:affiliation>Department of Pathology, Jean Perrin Cancer Center and ERTICa Research Group, University of Auvergne, Clermont-Ferrand, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Department of Pathology, Jean Perrin Cancer Center and ERTICa Research Group, University of Auvergne, Clermont-Ferrand</wicri:regionArea><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Auvergne (région administrative)</region><settlement type="city">Clermont-Ferrand</settlement></placeName></affiliation></author><author><name sortKey="Cox, David G" sort="Cox, David G" uniqKey="Cox D" first="David G" last="Cox">David G. Cox</name><affiliation wicri:level="3"><nlm:affiliation>Université de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Cancer Research Center of Lyon, Equipe Labellisée Ligue contre le Cancer, Lyon, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Université de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Cancer Research Center of Lyon, Equipe Labellisée Ligue contre le Cancer, Lyon</wicri:regionArea><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Lyon</settlement></placeName></affiliation></author><author><name sortKey="Hollande, Frederic" sort="Hollande, Frederic" uniqKey="Hollande F" first="Frédéric" last="Hollande">Frédéric Hollande</name><affiliation wicri:level="4"><nlm:affiliation>Department of Pathology, University of Melbourne, Parkville, Victoria, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Pathology, University of Melbourne, Parkville, Victoria</wicri:regionArea><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Ansieau, Stephane" sort="Ansieau, Stephane" uniqKey="Ansieau S" first="Stéphane" last="Ansieau">Stéphane Ansieau</name><affiliation wicri:level="3"><nlm:affiliation>Université de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Cancer Research Center of Lyon, Equipe Labellisée Ligue contre le Cancer, Lyon, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Université de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Cancer Research Center of Lyon, Equipe Labellisée Ligue contre le Cancer, Lyon</wicri:regionArea><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Lyon</settlement></placeName></affiliation></author><author><name sortKey="Caramel, Julie" sort="Caramel, Julie" uniqKey="Caramel J" first="Julie" last="Caramel">Julie Caramel</name><affiliation wicri:level="3"><nlm:affiliation>Université de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Cancer Research Center of Lyon, Equipe Labellisée Ligue contre le Cancer, Lyon, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Université de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Cancer Research Center of Lyon, Equipe Labellisée Ligue contre le Cancer, Lyon</wicri:regionArea><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Lyon</settlement></placeName></affiliation></author><author><name sortKey="Birnbaum, Daniel" sort="Birnbaum, Daniel" uniqKey="Birnbaum D" first="Daniel" last="Birnbaum">Daniel Birnbaum</name><affiliation wicri:level="3"><nlm:affiliation>Université Aix Marseille, CNRS, INSERM, Institut Paoli-Calmettes, CRCM, Molecular Oncology, Equipe labellisée Ligue Contre le Cancer, Marseille, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Université Aix Marseille, CNRS, INSERM, Institut Paoli-Calmettes, CRCM, Molecular Oncology, Equipe labellisée Ligue Contre le Cancer, Marseille</wicri:regionArea><placeName><region type="region">Provence-Alpes-Côte d'Azur</region><region type="old region">Provence-Alpes-Côte d'Azur</region><settlement type="city">Marseille</settlement></placeName></affiliation></author><author><name sortKey="Vigneron, Arnaud M" sort="Vigneron, Arnaud M" uniqKey="Vigneron A" first="Arnaud M" last="Vigneron">Arnaud M. Vigneron</name><affiliation wicri:level="3"><nlm:affiliation>Université de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Cancer Research Center of Lyon, Equipe Labellisée Ligue contre le Cancer, Lyon, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Université de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Cancer Research Center of Lyon, Equipe Labellisée Ligue contre le Cancer, Lyon</wicri:regionArea><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Lyon</settlement></placeName></affiliation></author><author><name sortKey="Tissier, Agnes" sort="Tissier, Agnes" uniqKey="Tissier A" first="Agnès" last="Tissier">Agnès Tissier</name><affiliation wicri:level="3"><nlm:affiliation>Université de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Cancer Research Center of Lyon, Equipe Labellisée Ligue contre le Cancer, Lyon, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Université de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Cancer Research Center of Lyon, Equipe Labellisée Ligue contre le Cancer, Lyon</wicri:regionArea><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Lyon</settlement></placeName></affiliation></author><author><name sortKey="Charafe Jauffret, Emmanuelle" sort="Charafe Jauffret, Emmanuelle" uniqKey="Charafe Jauffret E" first="Emmanuelle" last="Charafe-Jauffret">Emmanuelle Charafe-Jauffret</name><affiliation wicri:level="3"><nlm:affiliation>Université Aix Marseille, CNRS, INSERM, Institut Paoli-Calmettes, CRCM, Molecular Oncology, Equipe labellisée Ligue Contre le Cancer, Marseille, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Université Aix Marseille, CNRS, INSERM, Institut Paoli-Calmettes, CRCM, Molecular Oncology, Equipe labellisée Ligue Contre le Cancer, Marseille</wicri:regionArea><placeName><region type="region">Provence-Alpes-Côte d'Azur</region><region type="old region">Provence-Alpes-Côte d'Azur</region><settlement type="city">Marseille</settlement></placeName></affiliation></author><author><name sortKey="Puisieux, Alain" sort="Puisieux, Alain" uniqKey="Puisieux A" first="Alain" last="Puisieux">Alain Puisieux</name><affiliation wicri:level="3"><nlm:affiliation>Université de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Cancer Research Center of Lyon, Equipe Labellisée Ligue contre le Cancer, Lyon, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Université de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Cancer Research Center of Lyon, Equipe Labellisée Ligue contre le Cancer, Lyon</wicri:regionArea><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Lyon</settlement></placeName></affiliation></author></analytic><series><title level="j">Nature medicine</title><idno type="eISSN">1546-170X</idno><imprint><date when="2017" type="published">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adolescent</term><term>Adult</term><term>Aged</term><term>Aged, 80 and over</term><term>Animals</term><term>Breast Neoplasms (genetics)</term><term>Breast Neoplasms (metabolism)</term><term>Carcinoma (genetics)</term><term>Carcinoma (metabolism)</term><term>Cell Differentiation (genetics)</term><term>Cell Line, Tumor</term><term>Cell Transformation, Neoplastic (genetics)</term><term>Chromatin Immunoprecipitation</term><term>DNA Damage</term><term>Epithelial Cells (cytology)</term><term>Epithelial Cells (metabolism)</term><term>Female</term><term>Flow Cytometry</term><term>Fluorescent Antibody Technique</term><term>Gene Expression Profiling</term><term>Gene Expression Regulation, Neoplastic</term><term>Genomic Instability (genetics)</term><term>Humans</term><term>Immunoblotting</term><term>Mammary Glands, Human (cytology)</term><term>Methionine Sulfoxide Reductases (genetics)</term><term>Methionine Sulfoxide Reductases (metabolism)</term><term>Mice, Inbred NOD</term><term>Middle Aged</term><term>Reactive Oxygen Species</term><term>Real-Time Polymerase Chain Reaction</term><term>Sequence Analysis, DNA</term><term>Stem Cells (cytology)</term><term>Stem Cells (metabolism)</term><term>Tissue Array Analysis</term><term>Tumor Suppressor Protein p53 (genetics)</term><term>Tumor Suppressor Protein p53 (metabolism)</term><term>Young Adult</term><term>Zinc Finger E-box-Binding Homeobox 1 (genetics)</term><term>Zinc Finger E-box-Binding Homeobox 1 (metabolism)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Adolescent</term><term>Adulte</term><term>Adulte d'âge moyen</term><term>Altération de l'ADN</term><term>Analyse de profil d'expression de gènes</term><term>Analyse de séquence d'ADN</term><term>Analyse sur puce à tissus</term><term>Animaux</term><term>Carcinomes (génétique)</term><term>Carcinomes (métabolisme)</term><term>Cellules souches (cytologie)</term><term>Cellules souches (métabolisme)</term><term>Cellules épithéliales (cytologie)</term><term>Cellules épithéliales (métabolisme)</term><term>Cytométrie en flux</term><term>Différenciation cellulaire (génétique)</term><term>Espèces réactives de l'oxygène</term><term>Facteur de transcription Zeb1 (génétique)</term><term>Facteur de transcription Zeb1 (métabolisme)</term><term>Femelle</term><term>Glandes mammaires humaines (cytologie)</term><term>Humains</term><term>Immunoprécipitation de la chromatine</term><term>Immunotransfert</term><term>Instabilité du génome (génétique)</term><term>Jeune adulte</term><term>Lignée cellulaire tumorale</term><term>Methionine Sulfoxide Reductases (génétique)</term><term>Methionine Sulfoxide Reductases (métabolisme)</term><term>Protéine p53 suppresseur de tumeur (génétique)</term><term>Protéine p53 suppresseur de tumeur (métabolisme)</term><term>Réaction de polymérisation en chaine en temps réel</term><term>Régulation de l'expression des gènes tumoraux</term><term>Souris de lignée NOD</term><term>Sujet âgé</term><term>Sujet âgé de 80 ans ou plus</term><term>Technique d'immunofluorescence</term><term>Transformation cellulaire néoplasique (génétique)</term><term>Tumeurs du sein (génétique)</term><term>Tumeurs du sein (métabolisme)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Methionine Sulfoxide Reductases</term><term>Tumor Suppressor Protein p53</term><term>Zinc Finger E-box-Binding Homeobox 1</term></keywords><keywords scheme="MESH" qualifier="cytologie" xml:lang="fr"><term>Cellules souches</term><term>Cellules épithéliales</term><term>Glandes mammaires humaines</term></keywords><keywords scheme="MESH" qualifier="cytology" xml:lang="en"><term>Epithelial Cells</term><term>Mammary Glands, Human</term><term>Stem Cells</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Breast Neoplasms</term><term>Carcinoma</term><term>Cell Differentiation</term><term>Cell Transformation, Neoplastic</term><term>Genomic Instability</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Carcinomes</term><term>Différenciation cellulaire</term><term>Facteur de transcription Zeb1</term><term>Instabilité du génome</term><term>Methionine Sulfoxide Reductases</term><term>Protéine p53 suppresseur de tumeur</term><term>Transformation cellulaire néoplasique</term><term>Tumeurs du sein</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Breast Neoplasms</term><term>Carcinoma</term><term>Epithelial Cells</term><term>Methionine Sulfoxide Reductases</term><term>Stem Cells</term><term>Tumor Suppressor Protein p53</term><term>Zinc Finger E-box-Binding Homeobox 1</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Carcinomes</term><term>Cellules souches</term><term>Cellules épithéliales</term><term>Facteur de transcription Zeb1</term><term>Methionine Sulfoxide Reductases</term><term>Protéine p53 suppresseur de tumeur</term><term>Tumeurs du sein</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Adolescent</term><term>Adult</term><term>Aged</term><term>Aged, 80 and over</term><term>Animals</term><term>Cell Line, Tumor</term><term>Chromatin Immunoprecipitation</term><term>DNA Damage</term><term>Female</term><term>Flow Cytometry</term><term>Fluorescent Antibody Technique</term><term>Gene Expression Profiling</term><term>Gene Expression Regulation, Neoplastic</term><term>Humans</term><term>Immunoblotting</term><term>Mice, Inbred NOD</term><term>Middle Aged</term><term>Reactive Oxygen Species</term><term>Real-Time Polymerase Chain Reaction</term><term>Sequence Analysis, DNA</term><term>Tissue Array Analysis</term><term>Young Adult</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Adolescent</term><term>Adulte</term><term>Adulte d'âge moyen</term><term>Altération de l'ADN</term><term>Analyse de profil d'expression de gènes</term><term>Analyse de séquence d'ADN</term><term>Analyse sur puce à tissus</term><term>Animaux</term><term>Cytométrie en flux</term><term>Espèces réactives de l'oxygène</term><term>Femelle</term><term>Humains</term><term>Immunoprécipitation de la chromatine</term><term>Immunotransfert</term><term>Jeune adulte</term><term>Lignée cellulaire tumorale</term><term>Réaction de polymérisation en chaine en temps réel</term><term>Régulation de l'expression des gènes tumoraux</term><term>Souris de lignée NOD</term><term>Sujet âgé</term><term>Sujet âgé de 80 ans ou plus</term><term>Technique d'immunofluorescence</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Chromosomal instability (CIN), a feature of most adult neoplasms from their early stages onward, is a driver of tumorigenesis. However, several malignancy subtypes, including some triple-negative breast cancers, display a paucity of genomic aberrations, thus suggesting that tumor development may occur in the absence of CIN. Here we show that the differentiation status of normal human mammary epithelial cells dictates cell behavior after an oncogenic event and predetermines the genetic routes toward malignancy. Whereas oncogene induction in differentiated cells induces massive DNA damage, mammary stem cells are resistant, owing to a preemptive program driven by the transcription factor ZEB1 and the methionine sulfoxide reductase MSRB3. The prevention of oncogene-induced DNA damage precludes induction of the oncosuppressive p53-dependent DNA-damage response, thereby increasing stem cells' intrinsic susceptibility to malignant transformation. In accord with this model, a subclass of breast neoplasms exhibit unique pathological features, including high ZEB1 expression, a low frequency of TP53 mutations and low CIN.</div></front></TEI><affiliations><list><country><li>Australie</li><li>France</li></country><region><li>Auvergne (région administrative)</li><li>Auvergne-Rhône-Alpes</li><li>Provence-Alpes-Côte d'Azur</li><li>Rhône-Alpes</li><li>Victoria (État)</li><li>Île-de-France</li></region><settlement><li>Clermont-Ferrand</li><li>Lyon</li><li>Marseille</li><li>Melbourne</li><li>Orsay</li></settlement><orgName><li>Université Paris-Sud</li><li>Université de Melbourne</li></orgName></list><tree><country name="France"><region name="Auvergne-Rhône-Alpes"><name sortKey="Morel, Anne Pierre" sort="Morel, Anne Pierre" uniqKey="Morel A" first="Anne-Pierre" last="Morel">Anne-Pierre Morel</name></region><name sortKey="Ansieau, Stephane" sort="Ansieau, Stephane" uniqKey="Ansieau S" first="Stéphane" last="Ansieau">Stéphane Ansieau</name><name sortKey="Bertucci, Francois" sort="Bertucci, Francois" uniqKey="Bertucci F" first="François" last="Bertucci">François Bertucci</name><name sortKey="Birnbaum, Daniel" sort="Birnbaum, Daniel" uniqKey="Birnbaum D" first="Daniel" last="Birnbaum">Daniel Birnbaum</name><name sortKey="Cabaud, Olivier" sort="Cabaud, Olivier" uniqKey="Cabaud O" first="Olivier" last="Cabaud">Olivier Cabaud</name><name sortKey="Caramel, Julie" sort="Caramel, Julie" uniqKey="Caramel J" first="Julie" last="Caramel">Julie Caramel</name><name sortKey="Charafe Jauffret, Emmanuelle" sort="Charafe Jauffret, Emmanuelle" uniqKey="Charafe Jauffret E" first="Emmanuelle" last="Charafe-Jauffret">Emmanuelle Charafe-Jauffret</name><name sortKey="Chassot, Christelle" sort="Chassot, Christelle" uniqKey="Chassot C" first="Christelle" last="Chassot">Christelle Chassot</name><name sortKey="Combaret, Valerie" sort="Combaret, Valerie" uniqKey="Combaret V" first="Valérie" last="Combaret">Valérie Combaret</name><name sortKey="Cox, David G" sort="Cox, David G" uniqKey="Cox D" first="David G" last="Cox">David G. Cox</name><name sortKey="Despras, Emmanuelle" sort="Despras, Emmanuelle" uniqKey="Despras E" first="Emmanuelle" last="Despras">Emmanuelle Despras</name><name sortKey="Devouassoux Shisheboran, Mojgan" sort="Devouassoux Shisheboran, Mojgan" uniqKey="Devouassoux Shisheboran M" first="Mojgan" last="Devouassoux-Shisheboran">Mojgan Devouassoux-Shisheboran</name><name sortKey="Fauvet, Frederique" sort="Fauvet, Frederique" uniqKey="Fauvet F" first="Frédérique" last="Fauvet">Frédérique Fauvet</name><name sortKey="Finetti, Pascal" sort="Finetti, Pascal" uniqKey="Finetti P" first="Pascal" last="Finetti">Pascal Finetti</name><name sortKey="Ginestier, Christophe" sort="Ginestier, Christophe" uniqKey="Ginestier C" first="Christophe" last="Ginestier">Christophe Ginestier</name><name sortKey="Guitton, Jerome" sort="Guitton, Jerome" uniqKey="Guitton J" first="Jérôme" last="Guitton">Jérôme Guitton</name><name sortKey="Jauffret, Jean Luc" sort="Jauffret, Jean Luc" uniqKey="Jauffret J" first="Jean-Luc" last="Jauffret">Jean-Luc Jauffret</name><name sortKey="Lachuer, Joel" sort="Lachuer, Joel" uniqKey="Lachuer J" first="Joël" last="Lachuer">Joël Lachuer</name><name sortKey="Moyret Lalle, Caroline" sort="Moyret Lalle, Caroline" uniqKey="Moyret Lalle C" first="Caroline" last="Moyret-Lalle">Caroline Moyret-Lalle</name><name sortKey="Penault Llorca, Frederique" sort="Penault Llorca, Frederique" uniqKey="Penault Llorca F" first="Frédérique" last="Penault-Llorca">Frédérique Penault-Llorca</name><name sortKey="Pinatel, Christiane" sort="Pinatel, Christiane" uniqKey="Pinatel C" first="Christiane" last="Pinatel">Christiane Pinatel</name><name sortKey="Pommier, Roxane M" sort="Pommier, Roxane M" uniqKey="Pommier R" first="Roxane M" last="Pommier">Roxane M. Pommier</name><name sortKey="Puisieux, Alain" sort="Puisieux, Alain" uniqKey="Puisieux A" first="Alain" last="Puisieux">Alain Puisieux</name><name sortKey="Radosevic Robin, Nina" sort="Radosevic Robin, Nina" uniqKey="Radosevic Robin N" first="Nina" last="Radosevic-Robin">Nina Radosevic-Robin</name><name sortKey="Ruiz, Emmanuelle" sort="Ruiz, Emmanuelle" uniqKey="Ruiz E" first="Emmanuelle" last="Ruiz">Emmanuelle Ruiz</name><name sortKey="Saintigny, Pierre" sort="Saintigny, Pierre" uniqKey="Saintigny P" first="Pierre" last="Saintigny">Pierre Saintigny</name><name sortKey="Thomas, Emilie" sort="Thomas, Emilie" uniqKey="Thomas E" first="Emilie" last="Thomas">Emilie Thomas</name><name sortKey="Tissier, Agnes" sort="Tissier, Agnes" uniqKey="Tissier A" first="Agnès" last="Tissier">Agnès Tissier</name><name sortKey="Vigneron, Arnaud M" sort="Vigneron, Arnaud M" uniqKey="Vigneron A" first="Arnaud M" last="Vigneron">Arnaud M. Vigneron</name><name sortKey="Wang, Qing" sort="Wang, Qing" uniqKey="Wang Q" first="Qing" last="Wang">Qing Wang</name><name sortKey="Wicinski, Julien" sort="Wicinski, Julien" uniqKey="Wicinski J" first="Julien" last="Wicinski">Julien Wicinski</name><name sortKey="Wierinckx, Anne" sort="Wierinckx, Anne" uniqKey="Wierinckx A" first="Anne" last="Wierinckx">Anne Wierinckx</name></country><country name="Australie"><region name="Victoria (État)"><name sortKey="Hollande, Frederic" sort="Hollande, Frederic" uniqKey="Hollande F" first="Frédéric" last="Hollande">Frédéric Hollande</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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|texte= A stemness-related ZEB1-MSRB3 axis governs cellular pliancy and breast cancer genome stability.
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