Journal
EMBO REPORTS
Volume 14, Issue 4, Pages 356-363Publisher
WILEY
DOI: 10.1038/embor.2013.16
Keywords
telomere; TRF2; Wnt signalling; cancer
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Funding
- Association de la Recherche contre le Cancer (ARC)
- L'Institut National du Cancer (TELOFUN program)
- Agence Nationale de la Recherche (ANR)
- Ligue Nationale Contre le Cancer
- European Community [TELOMARKER Health-F2-2007-200950]
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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/beta-catenin signalling pathway in human cancer and normal cells as well as in mouse intestinal tissues. Furthermore, beta-catenin binds to TRF2 gene regulatory regions that are functional in a luciferase transactivating assay. Reduced beta-catenin expression in cancer cells triggers a marked increase in telomere dysfunction, which can be reversed by TRF2 overexpression. We conclude that the Wnt/beta-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.
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