Telomere protection and TRF2 expression are enhanced by the canonical Wnt signalling pathway

Irmina Diala (1, 2) , Nicole Wagner (1) , Frédérique Magdinier (3, 2) , Marina Shkreli (1) , Maria Sirakov (4) , Serge Bauwens (2) , Caroline Schluth-Bolard (2) , Thomas Simonet (2) , Valérie M Renault (1) , Jing Ye (1, 2, 5) , Abdelnnadir Djerbi (1) , Pascal Pineau (6) , Jinkuk Choi (7) , Steven Artandi (7) , Anne Dejean (6) , Michelina Plateroti (4) , Eric Gilson (1, 2, 8)

1 IRCAN - Institut de Recherche sur le Cancer et le Vieillissement
2 LBMC UMR 5239 - Laboratoire de biologie et modélisation de la cellule
3 GMGF - Génétique Médicale et Génomique Fonctionnelle
4 IGFL - Institut de Génomique Fonctionnelle de Lyon
5 Ruijin Hospital [Shanghai, Chine]
6 Organisation Nucléaire et Oncogenèse / Nuclear Organization and Oncogenesis
7 Department of Medicine [Stanford]
8 CHU - Hôpital Archet 2 [Nice]

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/b-catenin signalling pathway in human cancer and normal cells as well as in mouse intestinal tissues. Furthermore, b-catenin binds to TRF2 gene regulatory regions that are functional in a luciferase transactivat-ing assay. Reduced b-catenin expression in cancer cells triggers a marked increase in telomere dysfunction, which can be reversed by TRF2 overexpression. We conclude that the Wnt/b-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.

Keywords: Wnt signalling; cancer; telomere; TRF2

Domains: Life Sciences [q-bio]; Genetics

Irmina Diala, Nicole Wagner, Frédérique Magdinier, Marina Shkreli, Maria Sirakov, et al.. Telomere protection and TRF2 expression are enhanced by the canonical Wnt signalling pathway. EMBO Reports, 2013, 14 (4), pp.356 - 363. ⟨10.1038/embor.2013.16⟩. ⟨hal-01663630⟩