端粒保护和 TRF2 表达受经典 Wnt 信号通路增强。
Telomere protection and TRF2 expression are enhanced by the canonical Wnt signalling pathway.
机构信息
Faculté de Médecine de Nice, Institut for Research on Cancer and Aging, Nice (IRCAN), Nice University, Nice, France.
出版信息
EMBO Rep. 2013 Apr;14(4):356-63. doi: 10.1038/embor.2013.16. Epub 2013 Feb 22.
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.
摘要
DNA 结合蛋白 TRF2 对于哺乳动物端粒保护和染色体稳定性至关重要。我们在此表明，Wnt/β-catenin 信号通路在人类癌症和正常细胞以及小鼠肠道组织中激活了 TRF2 的表达。此外，β-catenin 与在荧光素酶转录激活测定中具有功能的 TRF2 基因调控区域结合。在癌细胞中减少 β-catenin 的表达会引发端粒功能障碍的显著增加，而 TRF2 的过表达可以逆转这种情况。我们的结论是，Wnt/β-catenin 信号通路维持了对端粒保护至关重要的 TRF2 水平。这在发育、成体干细胞功能和肿瘤发生过程中可能具有重要作用。
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