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

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

Research output: Contribution to journalArticle

297 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)427-442
Number of pages16
JournalCancer Cell
Volume20
Issue number4
DOIs
Publication statusPublished - 2011 Oct 18

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Catenins
Glioma
Carcinogenesis
Gene Expression
Cell Nucleus Active Transport
Neural Stem Cells
Neoplasms
Stem Cells
Mutation

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cell Biology
  • Cancer Research

Cite this

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, René H. ; He, Xi ; Huang, Suyun. / FoxM1 Promotes β-Catenin Nuclear Localization and Controls Wnt Target-Gene Expression and Glioma Tumorigenesis. In: Cancer Cell. 2011 ; Vol. 20, No. 4. pp. 427-442.
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Zhang, N, Wei, P, Gong, A, Chiu, WT, Lee, HT, Colman, H, Huang, H, Xue, J, Liu, M, Wang, Y, Sawaya, R, Xie, K, Yung, WKA, Medema, RH, He, X & Huang, S 2011, 'FoxM1 Promotes β-Catenin Nuclear Localization and Controls Wnt Target-Gene Expression and Glioma Tumorigenesis', Cancer Cell, vol. 20, no. 4, pp. 427-442. https://doi.org/10.1016/j.ccr.2011.08.016

FoxM1 Promotes β-Catenin Nuclear Localization and Controls Wnt Target-Gene Expression and Glioma Tumorigenesis. / 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, René H.; He, Xi; Huang, Suyun.

In: Cancer Cell, Vol. 20, No. 4, 18.10.2011, p. 427-442.

Research output: Contribution to journalArticle

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