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Telomere protection and TRF2 expression are enhanced by the canonical Wnt signalling pathway |
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| Authors: | Irmina Diala Nicole Wagner Frédérique Magdinier Marina Shkreli Serge Bauwens Caroline Schluth‐Bolard Thomas Simonet Valérie M Renault Jing Ye Abdelnnadir Djerbi Pascal Pineau Jinkuk Choi Steven Artandi Anne Dejean Eric Gilson |
| Affiliation: | 1. Faculté de Médecine de Nice, Institut for Research on Cancer and Aging, Nice (IRCAN), Nice University CNRS UMR7284/INSERM U1081, 28 Avenue de Valombrose, , Nice, F‐06107 France;2. Laboratory of Molecular Biology of the Cell, CNRS UMR5239, Ecole Normale Supérieure de Lyon, , Lyon, F‐69364 France;3. Laboratory of Medical Genetics and Functional Genomics, INSERM UMR_S 910, Aix‐Marseille University, La Timone Faculty of Medicine, , Marseille, F‐13385 France;4. Shanghai Jiatong University, Shanghai Ruijin Hospital, , Shanghai, 200025 China;5. Nuclear Organisation and Oncogenesis Unit/INSERM U993, Institut Pasteur, , Paris, F‐75015 France;6. Department of Medicine, Stanford University School of Medicine, , Stanford, California, 94305 USA;7. Department of Medical Genetics, Archet 2 Hospital, CHU of Nice, , Nice, F‐06202 France |
| 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. |
| Keywords: | telomere TRF2 Wnt signalling cancer |