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Telomere protection and TRF2 expression are enhanced by the canonical Wnt signalling pathway
Author(s) -
Diala Irmina,
Wagner Nicole,
Magdinier Frédérique,
Shkreli Marina,
Sirakov Maria,
Bauwens Serge,
SchluthBolard Caroline,
Simonet Thomas,
Renault Valérie M,
Ye Jing,
Djerbi Abdelnnadir,
Pineau Pascal,
Choi Jinkuk,
Artandi Steven,
Dejean Anne,
Plateroti Michelina,
Gilson Eric
Publication year - 2013
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/embor.2013.16
Subject(s) - telomere , wnt signaling pathway , microbiology and biotechnology , carcinogenesis , biology , hedgehog signaling pathway , catenin , signal transduction , gene , cancer research , genetics
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.