Author/Authors :
Zhang، نويسنده , , Nu and Wei، نويسنده , , Ping and Gong، نويسنده , , Aihua and Chiu، نويسنده , , Wen-Tai and Lee، نويسنده , , Hsueh-Te and Colman، نويسنده , , Howard and Huang، نويسنده , , He and Xue، نويسنده , , Jianfei and Liu، نويسنده , , Mingguang and Wang، نويسنده , , Yong and Sawaya، نويسنده , , Raymond and Xie، نويسنده , , Keping and Yung، نويسنده , , W.K. Alfred and Medema، نويسنده , , René H. and He، نويسنده , , Xi and Huang، نويسنده , , Suyun، نويسنده ,
Abstract :
Summary
catenin signaling is essential for stem cell regulation and tumorigenesis, but its molecular mechanisms are not fully understood. Here, we report that FoxM1 is a downstream component of Wnt signaling and is critical for β-catenin transcriptional function in tumor cells. Wnt3a increases the level and nuclear translocation of FoxM1, which binds directly to β-catenin and enhances β-catenin nuclear localization and transcriptional activity. Genetic deletion of FoxM1 in immortalized neural stem cells abolishes β-catenin nuclear localization. FoxM1 mutations that disrupt the FoxM1–β-catenin interaction or FoxM1 nuclear import prevent β-catenin nuclear accumulation in tumor cells. FoxM1–β-catenin interaction controls Wnt target gene expression, is required for glioma formation, and represents a mechanism for canonical Wnt signaling during tumorigenesis.
