Bmi1 is essential in Twist1-induced epithelial–mesenchymal transition
Author: ["Muh-Hwa Yang","Dennis Shin-Shian Hsu","Hsei-Wei Wang","Hsiao-Jung Wang","Hsin-Yi Lan","Wen-Hao Yang","Chi-Hung Huang","Shou-Yen Kao","Cheng-Hwai Tzeng","Shyh-Kuan Tai","Shyue-Yih Chang","Oscar Kuang-Sheng Lee","Kou-Juey Wu"]
Publication: Nature Cell Biology
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Abstract
The transcription factor Twist1 interacts with the Bmi1 polycomb group protein. This complex is proposed to regulate the epithelial–mesenchymal transition and the tumour-initiating capability of head-and-neck squamous cell carcinoma cells. The epithelial–mesenchymal transition (EMT), one of the main mechanisms underlying development of cancer metastasis, induces stem-like properties in epithelial cells. Bmi1 is a polycomb-group protein that maintains self-renewal, and is frequently overexpressed in human cancers. Here, we show the direct regulation of BMI1 by the EMT regulator, Twist1. Furthermore, Twist1 and Bmi1 were mutually essential to promote EMT and tumour-initiating capability. Twist1 and Bmi1 act cooperatively to repress expression of both E-cadherin and p16INK4a. In patients with head and neck cancers, increased levels of both Twist1 and Bmi1 correlated with downregulation of E-cadherin and p16INK4a, and was associated with the worst prognosis. These results suggest that Twist1-induced EMT and tumour-initiating capability in cancer cells occurs through chromatin remodelling, which leads to unfavourable clinical outcomes.
Cite this article
Yang, MH., Hsu, DS., Wang, HW. et al. Bmi1 is essential in Twist1-induced epithelial–mesenchymal transition. Nat Cell Biol 12, 982–992 (2010). https://doi.org/10.1038/ncb2099
