title: Telomere protection and TRF2 expression are enhanced by the canonical Wnt signalling pathway.
abstract: The DNA-binding protein TRF2 is essential for telomere protection and chromosome stability in mammals. We show here that TRF2 expression is activated by the Wnt/β-catenin signalling pathway in human cancer and normal cells as well as in mouse intestinal tissues. Furthermore, β-catenin binds to TRF2 gene regulatory regions that are functional in a luciferase transactivating assay. Reduced β-catenin expression in cancer cells triggers a marked increase in telomere dysfunction, which can be reversed by TRF2 overexpression. We conclude that the Wnt/β-catenin signalling pathway maintains a level of TRF2 critical for telomere protection. This is expected to have an important role during development, adult stem cell function and oncogenesis.
authors: Faculté de Médecine de Nice, Institut for Research on Cancer and Aging, Nice (IRCAN), Nice University, Nice, France.
authors: Irmina
authors: I
authors: Diala
authors: Nicole
authors: N
authors: Wagner
authors: Frédérique
authors: F
authors: Magdinier
authors: Marina
authors: M
authors: Shkreli
authors: Maria
authors: M
authors: Sirakov
authors: Serge
authors: S
authors: Bauwens
authors: Caroline
authors: C
authors: Schluth-Bolard
authors: Thomas
authors: T
authors: Simonet
authors: Valérie M
authors: VM
authors: Renault
authors: Jing
authors: J
authors: Ye
authors: Abdelnnadir
authors: A
authors: Djerbi
authors: Pascal
authors: P
authors: Pineau
authors: Jinkuk
authors: J
authors: Choi
authors: Steven
authors: S
authors: Artandi
authors: Anne
authors: A
authors: Dejean
authors: Michelina
authors: M
authors: Plateroti
authors: Eric
authors: E
authors: Gilson
mesh_terms: D000818:Animals; D001665:Binding Sites; D005260:Female; D015870:Gene Expression; D005786:Gene Expression Regulation; D045325:HCT116 Cells; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D059505:Telomere Homeostasis; D035341:Telomeric Repeat Binding Protein 2 / Q000235:genetics / Q000378:metabolism*; D059467:Transcriptome; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000378:metabolism
chemical_list: C495270:CTNNB1 protein, human; D012333:RNA, Messenger; C504753:TERF2 protein, human; D035341:Telomeric Repeat Binding Protein 2; D051176:beta Catenin