FoxM1 Promotes β-Catenin Nuclear Localization and Controls Wnt Target-Gene Expression and Glioma Tumorigenesis

作者：Zhang, Nu; Wei, Ping; Gong, Aihua; Chiu, Wen-Tai; Lee, Hsueh-Te; Colman, Howard; Huang, He; Xue, Jianfei; Liu, Mingguang; Wang, Yong; Sawaya, Raymond; Xie, Keping; Yung, W. K. Alfred; Medema, Rene H.; He, Xi; Huang, Suyun^*

来源：Cancer Cell, 2011, 20(4): 427-442.

DOI：10.1016/j.ccr.2011.08.016

• TRANSCRIPTION FACTOR
• NEURAL STEM
• CELL
• TUMORS
• IDENTIFICATION
• GLIOBLASTOMAS
• APC

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

• 出版日期2011-10-18
• 单位复旦大学; 中山大学