FoxM1促进β- catenin的细胞核定位和控制Wnt信号靶基因的表达与神经胶质瘤发生

Cancer Cell 2011 Oct;20(4):427-42. [IF:26.925]

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

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 WK , Medema RH , He X , Huang S .

Department of Neurosurgery, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA; Department of Neurosurgery, The 1st Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

广州市中山大学第一附属医院神经外科，美国德州大学MD安德森癌症中心

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.