2014
DOI: 10.1016/j.celrep.2014.09.038
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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. Instea… Show more

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Cited by 72 publications
(95 citation statements)
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“…The decrease in VEGF expression and the increase in CXCL9 and CXCL10 expression may account for the impaired vascularization of experimental tumors [23]. The implication of TERF2 in angiogenic processes has been described recently through direct regulation of the platelet-derived growth factor receptor β in endothelial cells, but not directly in the tumor cells [35]. TERF2 high expression levels correlate with lower expression of a variety of pro-inflammatory and immune system activating cytokines (IL6, IL8/CXCL8, RANTES/CCL5 and GRO/CXCL1).…”
Section: Discussionmentioning
confidence: 99%
“…The decrease in VEGF expression and the increase in CXCL9 and CXCL10 expression may account for the impaired vascularization of experimental tumors [23]. The implication of TERF2 in angiogenic processes has been described recently through direct regulation of the platelet-derived growth factor receptor β in endothelial cells, but not directly in the tumor cells [35]. TERF2 high expression levels correlate with lower expression of a variety of pro-inflammatory and immune system activating cytokines (IL6, IL8/CXCL8, RANTES/CCL5 and GRO/CXCL1).…”
Section: Discussionmentioning
confidence: 99%
“…As a separate consideration, some shelterin components function within the same extratelomeric regulatory networks as TERT. Indeed, TRF2 expression is regulated by Wnt signaling [61] and excess TRF2 promotes angiogenesis by binding directly to the promoter of the platelet-derived growth factor receptor-β (PDGFRβ; [133]). Moreover, TIN2 is localized to telomeres via its interaction with TPP1 and abolishing this interaction targets TIN2 to mitochondria where it regulates energy metabolism and oxidative stress response [134].…”
Section: Telomerase: More Than a Telomere Machinementioning
confidence: 99%
“…There are also increasing pieces of evidence showing that TRF2 is also involved in extra-telomeric functions (15). By combining chromatin immunoprecipitation with high-throughput DNA sequencing (ChIP-Seq), TRF2 was shown to occupy a set of interstitial telomeric sequences (ITSs), where it can act as a transcriptional activator (1619). Another transcriptional activity of TRF2 relies on its binding to the Repressor Element 1-Silencing Transcription factor (REST) involved in the regulation of neural differentiation (2022).…”
Section: Introductionmentioning
confidence: 99%
“…In contrast, TRF2 is up-regulated in many cancers (1819,35–39) where it appears to be directly regulated by the canonical Wnt/b-catenin and WT1 pathways (19,40). In cancer cells, TRF2 can promote oncogenesis by a cell extrinsic mechanism involving Natural Killer cell inhibition through the binding and the activation of the ITS-containing HS3ST4 gene encoding for the heparan sulphate (glucosamine) 3-O-sulphotransferase (18,41).…”
Section: Introductionmentioning
confidence: 99%