title: DDB2 (damaged-DNA binding 2) protein: a new modulator of nanomechanical properties and cell adhesion of breast cancer cells.
abstract: DDB2, known for its role in DNA repair, was recently shown to reduce mammary tumor invasiveness by inducing the transcription of IκBα, an inhibitor of NF-κB activity. Since cellular adhesion is a key event during the epithelial to mesenchymal transition (EMT) leading to the invasive capacities of breast tumor cells, the aim of this study was to investigate the role of DDB2 in this process. Thus, using low and high DDB2-expressing MDA-MB231 and MCF7 cells, respectively, in which DDB2 expression was modulated experimentally, we showed that DDB2 overexpression was associated with a decrease of adhesion abilities on glass and plastic areas of breast cancer cells. Then, we investigated cell nanomechanical properties by atomic force microscopy (AFM). Our results revealed significant changes in the Young's Modulus value and the adhesion force in MDA-MB231 and MCF7 cells, whether DDB2 was expressed or not. The cell stiffness decrease observed in MDA-MB231 and MCF7 expressing DDB2 was correlated with a loss of the cortical actin-cytoskeleton staining. To understand how DDB2 regulates these processes, an adhesion-related gene PCR-Array was performed. Several adhesion-related genes were differentially expressed according to DDB2 expression, indicating that important changes are occurring at the molecular level. Thus, this work demonstrates that AFM technology is an important tool to follow cellular changes during tumorigenesis. Moreover, our data revealed that DDB2 is involved in early events occurring during metastatic progression of breast cancer cells and will contribute to define this protein as a new marker of metastatic progression in this type of cancer.
authors.affiliation: Université de Lorraine, Centre de Recherche en Automatique de Nancy, CRAN, UMR 7039, Vandœuvre-lès-Nancy, F-54506, France. stephanie.grandemange@univ-lorraine.fr gregory.francius@univ-lorraine.fr and CNRS, Centre de Recherche en Automatique de Nancy, CRAN, UMR 7039, Vandœuvre-lès-Nancy, F-54506, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Barbieux
authors.affiliation: Université de Lorraine, Laboratoire de Chimie Physique et Microbiologie pour l'Environnement, LCPME, UMR 7564, Villers-lès-Nancy, F-54600, France. gregory.francius@univ-lorraine.fr and CNRS, Laboratoire de Chimie Physique et Microbiologie pour l'Environnement, LCPME, UMR 7564, Villers-lès-Nancy, F-54600, France.
authors.forename: Jalal
authors.initials: J
authors.lastname: Bacharouche
authors.affiliation: Université de Lorraine, Centre de Recherche en Automatique de Nancy, CRAN, UMR 7039, Vandœuvre-lès-Nancy, F-54506, France. stephanie.grandemange@univ-lorraine.fr gregory.francius@univ-lorraine.fr and CNRS, Centre de Recherche en Automatique de Nancy, CRAN, UMR 7039, Vandœuvre-lès-Nancy, F-54506, France.
authors.forename: Charles
authors.initials: C
authors.lastname: Soussen
authors.affiliation: CNRS, FR3209 Biologie Moléculaire Cellulaire et Thérapeutique (BMCT), Plateforme d'Imagerie Cellulaire et Tissulaire PTIBC-IBISA, Biopôle de l'Université de Lorraine, Campus Biologie-Santé, Vandœuvre-lès-Nancy, F-54506, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Hupont
authors.affiliation: Université de Lorraine, Laboratoire Interdisciplinaire des Environnements Continentaux, LIEC, UMR 7360, Vandœuvre-lès-Nancy, F-54500, France and CNRS, Laboratoire Interdisciplinaire des Environnements Continentaux, LIEC, UMR 7360, Vandœuvre-lès-Nancy, F-54500, France.
authors.forename: Angélina
authors.initials: A
authors.lastname: Razafitianamaharavo
authors.affiliation: Université de Lorraine, Centre de Recherche en Automatique de Nancy, CRAN, UMR 7039, Vandœuvre-lès-Nancy, F-54506, France. stephanie.grandemange@univ-lorraine.fr gregory.francius@univ-lorraine.fr and CNRS, Centre de Recherche en Automatique de Nancy, CRAN, UMR 7039, Vandœuvre-lès-Nancy, F-54506, France.
authors.forename: Rémi
authors.initials: R
authors.lastname: Klotz
authors.affiliation: Université de Lorraine, Centre de Recherche en Automatique de Nancy, CRAN, UMR 7039, Vandœuvre-lès-Nancy, F-54506, France. stephanie.grandemange@univ-lorraine.fr gregory.francius@univ-lorraine.fr and CNRS, Centre de Recherche en Automatique de Nancy, CRAN, UMR 7039, Vandœuvre-lès-Nancy, F-54506, France.
authors.forename: Rémi
authors.initials: R
authors.lastname: Pannequin
authors.affiliation: Université de Lorraine, Centre de Recherche en Automatique de Nancy, CRAN, UMR 7039, Vandœuvre-lès-Nancy, F-54506, France. stephanie.grandemange@univ-lorraine.fr gregory.francius@univ-lorraine.fr and CNRS, Centre de Recherche en Automatique de Nancy, CRAN, UMR 7039, Vandœuvre-lès-Nancy, F-54506, France.
authors.forename: David
authors.initials: D
authors.lastname: Brie
authors.affiliation: Université de Lorraine, Centre de Recherche en Automatique de Nancy, CRAN, UMR 7039, Vandœuvre-lès-Nancy, F-54506, France. stephanie.grandemange@univ-lorraine.fr gregory.francius@univ-lorraine.fr and CNRS, Centre de Recherche en Automatique de Nancy, CRAN, UMR 7039, Vandœuvre-lès-Nancy, F-54506, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Bécuwe
authors.affiliation: Université de Lorraine, Laboratoire de Chimie Physique et Microbiologie pour l'Environnement, LCPME, UMR 7564, Villers-lès-Nancy, F-54600, France. gregory.francius@univ-lorraine.fr and CNRS, Laboratoire de Chimie Physique et Microbiologie pour l'Environnement, LCPME, UMR 7564, Villers-lès-Nancy, F-54600, France.
authors.forename: Grégory
authors.initials: G
authors.lastname: Francius
authors.affiliation: Université de Lorraine, Centre de Recherche en Automatique de Nancy, CRAN, UMR 7039, Vandœuvre-lès-Nancy, F-54506, France. stephanie.grandemange@univ-lorraine.fr gregory.francius@univ-lorraine.fr and CNRS, Centre de Recherche en Automatique de Nancy, CRAN, UMR 7039, Vandœuvre-lès-Nancy, F-54506, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Grandemange
mesh_terms: D001943:Breast Neoplasms / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D002448:Cell Adhesion; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D055119:Elastic Modulus; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D061986:MCF-7 Cells; D018625:Microscopy, Atomic Force; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000096:biosynthesis*
chemical_list: C117669:DDB2 protein, human; D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins