FoxM1 promotes ?-catenin nuclear localization and controls Wnt target-gene expression and glioma tumorigenesis.

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

SUBMITTER: Zhang N 

PROVIDER: S-EPMC3199318 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature