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Cancer Cell. 2011 Oct 18;20(4):427-42. doi: 10.1016/j.ccr.2011.08.016.

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

Author information

1
Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

Abstract

Wnt/β-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.

PMID:
22014570
PMCID:
PMC3199318
DOI:
10.1016/j.ccr.2011.08.016
[Indexed for MEDLINE]
Free PMC Article

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