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Cell Rep. 2014 Nov 6;9(3):1047-60. doi: 10.1016/j.celrep.2014.09.038. Epub 2014 Oct 23.

The Telomeric Protein TRF2 Regulates Angiogenesis by Binding and Activating the PDGFRβ Promoter.

Author information

1
Institut for Research on Cancer and Aging, Nice (IRCAN), University of Nice Sophia-Antipolis, CNRS UMR7284/INSERM U1081, Faculty of Medicine, 06107 Nice, France.
2
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.
3
Department of Pathology, Le Centre Hospitalier Universitaire de Nice, 06107 Nice, France.
4
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.
5
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.

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.

PMID:
25437559
DOI:
10.1016/j.celrep.2014.09.038
[Indexed for MEDLINE]
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