FoxM1 Promotes β-catenin Nuclear Localization and Controls Wnt Target-gene Expression and Glioma Tumorigenesis

Overview

Journal Cancer Cell

Publisher Cell Press

Specialty Oncology

Date 2011 Oct 22

PMID 22014570

Citations 344

Authors

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

Rene H Medema

Xi He

Suyun Huang

Affiliations

Soon will be listed here.

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.

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