FoxM1 Promotes ²-Catenin Nuclear Localization and Controls Wnt Target-Gene Expression and Glioma Tumorigenesis
Menée in vitro, cette étude identifie un mécanisme impliquant la protéine FoxM1 dans la progression d'un glioblastome
Wnt/²-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 ²-catenin transcriptional function in tumor cells. Wnt3a increases the level and nuclear translocation of FoxM1, which binds directly to ²-catenin and enhances ²-catenin nuclear localization and transcriptional activity. Genetic deletion of FoxM1 in immortalized neural stem cells abolishes ²-catenin nuclear localization. FoxM1 mutations that disrupt the FoxM1 ²-catenin interaction or FoxM1 nuclear import prevent ²-catenin nuclear accumulation in tumor cells. FoxM1 ²-catenin interaction controls Wnt target gene expression, is required for glioma formation, and represents a mechanism for canonical Wnt signaling during tumorigenesis. º FoxM1 binds ²-catenin and promotes its nuclear localization º FoxM1 is required for ²-catenin activation and the expression of Wnt target genes º FoxM1 is a downstream component of canonical Wnt signaling pathway º FoxM1 ²-catenin interaction controls Wnt target gene expression and tumorigenesis
Cancer cell , résumé, 2010