Bmi1 is essential in Twist1-induced epithelial–mesenchymal transition

• Published in: Nature cell biology Vol. 12; no. 10; pp. 982 - 992
• Main Authors: Yang, Muh-Hwa, Hsu, Dennis Shin-Shian, Wang, Hsei-Wei, Wang, Hsiao-Jung, Lan, Hsin-Yi, Yang, Wen-Hao, Huang, Chi-Hung, Kao, Shou-Yen, Tzeng, Cheng-Hwai, Tai, Shyh-Kuan, Chang, Shyue-Yih, Lee, Oscar Kuang-Sheng, Wu, Kou-Juey
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.10.2010; Nature Publishing Group
• Subjects: 631/208/200; 631/80/84/2176; 692/699/67/1536; Cadherins - genetics; Cadherins - metabolism; Cancer; Cancer Research; Care and treatment; Cell Biology; Cell Line; Cell Transformation, Neoplastic - genetics; Chromatin; Chromatin Assembly and Disassembly; Developmental Biology; Down-Regulation; Epithelial cells; Epithelial Cells - metabolism; Epithelial Cells - pathology; Exons - genetics; Female; Genes, p16; Head and Neck Neoplasms - genetics; Head and Neck Neoplasms - metabolism; Head and Neck Neoplasms - pathology; Humans; Hypoxia; Life Sciences; Male; Mesoderm - metabolism; Mesoderm - pathology; Metastasis; Middle Aged; Neoplasm Metastasis - genetics; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Physiological aspects; Polycomb Repressive Complex 1; Prognosis; Promoter Regions, Genetic - genetics; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins - metabolism; Repressor Proteins - genetics; Repressor Proteins - metabolism; Stem Cells; Transcription, Genetic; Tumors; Twist-Related Protein 1 - genetics; Twist-Related Protein 1 - metabolism; Taiwan
• ISSN: 1465-7392; 1476-4679; 1476-4679
• DOI: 10.1038/ncb2099

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.