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/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.