title: The actin cytoskeleton-associated protein zyxin acts as a tumor suppressor in Ewing tumor cells.
abstract: Changes in cell architecture, essentially linked to profound cytoskeleton rearrangements, are common features accompanying cell transformation. Supporting the involvement of the microfilament network in tumor cell behavior, several actin-binding proteins, including zyxin, a potential regulator of actin polymerization, may play a role in oncogenesis. In this work, we investigate the status of zyxin in Ewing tumors, a family of pediatric malignancies of bone and soft tissues, which are mainly associated with a t(11;22) chromosomal translocation encoding the EWS-FLI1 oncoprotein. We observe that EWS-FLI1-transformed murine fibroblasts, as well as human Ewing tumor-derived SK-N-MC cells, exhibit a complete disruption of their actin cytoskeleton, retaining very few stress fibers, focal adhesions and cell-to-cell contacts. We show that within these cells, zyxin is expressed at very low levels and remains diffusely distributed throughout the cytoplasm, instead of concentrating in actin-rich dynamic structures. We demonstrate that zyxin gene transfer into EWS-FLI1-transformed fibroblasts elicits reconstitution of zyxin-rich focal adhesions and intercellular junctions, dramatic reorganization of the actin cytoskeleton, decreased cell motility, inhibition of anchorage-independent growth and impairment of tumor formation in athymic mice. We observe similar phenotypic changes after zyxin gene transfer in SK-N-MC cells, suggesting that zyxin has tumor suppressor activity in Ewing tumor cells.
authors.affiliation: Laboratoire de Biotechnologie et Pharmacologie génétique appliquée, CNRS UMR 8113, Ecole Normale Supérieure de Cachan, 61 avenue du Président Wilson, 94230 Cachan, France. vamsel@igr.fr
authors.forename: Valérie
authors.initials: V
authors.lastname: Amsellem
authors.forename: Marie-Hélène
authors.initials: MH
authors.lastname: Kryszke
authors.forename: Martial
authors.initials: M
authors.lastname: Hervy
authors.forename: Frédéric
authors.initials: F
authors.lastname: Subra
authors.forename: Rafika
authors.initials: R
authors.lastname: Athman
authors.forename: Hervé
authors.initials: H
authors.lastname: Leh
authors.forename: Corinne
authors.initials: C
authors.lastname: Brachet-Ducos
authors.forename: Christian
authors.initials: C
authors.lastname: Auclair
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D001859:Bone Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002454:Cell Differentiation / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D003598:Cytoskeletal Proteins; D022001:Focal Adhesions / Q000378:metabolism; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007365:Intercellular Junctions / Q000378:metabolism; D051379:Mice; D041681:NIH 3T3 Cells; D034802:RNA-Binding Protein EWS / Q000235:genetics; D012512:Sarcoma, Ewing / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D014162:Transfection; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D060589:Zyxin
chemical_list: D003598:Cytoskeletal Proteins; D006023:Glycoproteins; D034802:RNA-Binding Protein EWS; D025521:Tumor Suppressor Proteins; C092842:ZYX protein, human; D060589:Zyxin