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

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• 作者：Nu Zhang¹ ;   ; ⁵ ;   ; ⁹ ; Ping Wei¹ ;   ; ⁶ ;   ; ⁹ ; Aihua Gong¹ ; Wen-Tai Chiu¹ ; Hsueh-Te Lee¹ ; Howard Colman² ; He Huang⁸ ; Jianfei Xue¹ ; Mingguang Liu¹ ; Yong Wang¹ ; Raymond Sawaya¹ ; Keping Xie³ ;   ; ⁴ ; W.K.  ; Alfred Yung² ; René ;   ; H. Medema⁷ ; Xi He⁸ ; Suyun Huang¹ ;   ; ⁴ ;   ; ^{suhuang@mdanderson.org}
• 刊名：Cancer Cell
• 出版年：2011
• 出版时间：18 October 2011
• 年：2011
• 卷：20
• 期：4
• 页码：427-442
• 全文大小：2573 K

文摘

Summary

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