title: The Telomeric Protein TRF2 Regulates Angiogenesis by Binding and Activating the PDGFRβ Promoter.
abstract: Telomeric repeat binding factor 2 (TRF2), which plays a central role in telomere capping, is frequently increased in human tumors. We reveal here that TRF2 is expressed in the vasculature of most human cancer types, where it colocalizes with the Wilms' tumor suppressor WT1. We further show that TRF2 is a transcriptional target of WT1 and is required for proliferation, migration, and tube formation of endothelial cells. These angiogenic effects of TRF2 are uncoupled from its function in telomere capping. Instead, TRF2 binds and transactivates the promoter of the angiogenic tyrosine kinase platelet-derived growth factor receptor β (PDGFRβ). These findings reveal an unexpected role of TRF2 in neoangiogenesis and delineate a distinct function of TRF2 as a transcriptional regulator.
authors.affiliation: Institut for Research on Cancer and Aging, Nice (IRCAN), University of Nice Sophia-Antipolis, CNRS UMR7284/INSERM U1081, Faculty of Medicine, 06107 Nice, France.
authors.forename: Mounir
authors.initials: M
authors.lastname: El Maï
authors.affiliation: Institut for Research on Cancer and Aging, Nice (IRCAN), University of Nice Sophia-Antipolis, CNRS UMR7284/INSERM U1081, Faculty of Medicine, 06107 Nice, France.
authors.forename: Kay-Dietrich
authors.initials: KD
authors.lastname: Wagner
authors.affiliation: Institut for Research on Cancer and Aging, Nice (IRCAN), University of Nice Sophia-Antipolis, CNRS UMR7284/INSERM U1081, Faculty of Medicine, 06107 Nice, France; Department of Pathology, Le Centre Hospitalier Universitaire de Nice, 06107 Nice, France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Michiels
authors.affiliation: Institut for Research on Cancer and Aging, Nice (IRCAN), University of Nice Sophia-Antipolis, CNRS UMR7284/INSERM U1081, Faculty of Medicine, 06107 Nice, France; Department of Pathology, Le Centre Hospitalier Universitaire de Nice, 06107 Nice, France.
authors.forename: Damien
authors.initials: D
authors.lastname: Ambrosetti
authors.affiliation: Department of Pathology, Le Centre Hospitalier Universitaire de Nice, 06107 Nice, France.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Borderie
authors.affiliation: Department of Pathology, Le Centre Hospitalier Universitaire de Nice, 06107 Nice, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Destree
authors.affiliation: Institut for Research on Cancer and Aging, Nice (IRCAN), University of Nice Sophia-Antipolis, CNRS UMR7284/INSERM U1081, Faculty of Medicine, 06107 Nice, France.
authors.forename: Valerie
authors.initials: V
authors.lastname: Renault
authors.affiliation: Institut for Research on Cancer and Aging, Nice (IRCAN), University of Nice Sophia-Antipolis, CNRS UMR7284/INSERM U1081, Faculty of Medicine, 06107 Nice, France.
authors.forename: Nadir
authors.initials: N
authors.lastname: Djerbi
authors.affiliation: Institut for Research on Cancer and Aging, Nice (IRCAN), University of Nice Sophia-Antipolis, CNRS UMR7284/INSERM U1081, Faculty of Medicine, 06107 Nice, France.
authors.forename: Marie-Josèphe
authors.initials: MJ
authors.lastname: Giraud-Panis
authors.affiliation: Institut for Research on Cancer and Aging, Nice (IRCAN), University of Nice Sophia-Antipolis, CNRS UMR7284/INSERM U1081, Faculty of Medicine, 06107 Nice, France; Department of Medical Genetics, Le Centre Hospitalier Universitaire de Nice, 06107 Nice, France. Electronic address: eric.gilson@unice.fr.
authors.forename: Eric
authors.initials: E
authors.lastname: Gilson
authors.affiliation: Institut for Research on Cancer and Aging, Nice (IRCAN), University of Nice Sophia-Antipolis, CNRS UMR7284/INSERM U1081, Faculty of Medicine, 06107 Nice, France. Electronic address: nwagner@unice.fr.
authors.forename: Nicole
authors.initials: N
authors.lastname: Wagner
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D004249:DNA Damage; D004260:DNA Repair; D055786:Gene Knockout Techniques; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000098:blood supply / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000235:genetics* / Q000473:pathology; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000235:genetics*; D016615:Telomere / Q000378:metabolism; D035341:Telomeric Repeat Binding Protein 2 / Q000378:metabolism*; D015854:Up-Regulation / Q000235:genetics; D025721:WT1 Proteins / Q000378:metabolism
chemical_list: C504753:TERF2 protein, human; C534796:TRF2 protein, mouse; D035341:Telomeric Repeat Binding Protein 2; D025721:WT1 Proteins; D020797:Receptor, Platelet-Derived Growth Factor beta