文摘
Summary
Wnt/¦Â-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 ¦Â-catenin transcriptional function in tumor cells. Wnt3a increases the level and nuclear translocation of FoxM1, which binds directly to ¦Â-catenin and enhances ¦Â-catenin nuclear localization and transcriptional activity. Genetic deletion of FoxM1 in immortalized neural stem cells abolishes ¦Â-catenin nuclear localization. FoxM1 mutations that disrupt the FoxM1¨C?catenin interaction or FoxM1 nuclear import prevent ¦Â-catenin nuclear accumulation in tumor cells. FoxM1¨C?catenin interaction controls Wnt target gene expression, is required for glioma formation, and represents a mechanism for canonical Wnt signaling during tumorigenesis.