FoxM1 promotes ?-catenin nuclear localization and controls Wnt target-gene expression and glioma tumorigenesis.
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.
Mesh Terms:
Animals, Brain Neoplasms, Cell Line, Tumor, Cell Transformation, Neoplastic, Forkhead Box Protein M1, Forkhead Transcription Factors, Gene Expression Regulation, Neoplastic, Glioma, Humans, Mice, Mice, Nude, Signal Transduction, Wnt Proteins, beta Catenin
Animals, Brain Neoplasms, Cell Line, Tumor, Cell Transformation, Neoplastic, Forkhead Box Protein M1, Forkhead Transcription Factors, Gene Expression Regulation, Neoplastic, Glioma, Humans, Mice, Mice, Nude, Signal Transduction, Wnt Proteins, beta Catenin
Cancer Cell
Date: Oct. 18, 2011
PubMed ID: 22014570
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