Bmi1 is essential in Twist1-induced epithelial-mesenchymal transition

被引：555

作者：

Yang, Muh-Hwa ^{[1
,2
,3
,4
]}

Hsu, Dennis Shin-Shian ^{[1
]}

Wang, Hsei-Wei ^{[1
,4
,5
]}

Wang, Hsiao-Jung ^{[1
]}

Lan, Hsin-Yi ^{[1
]}

Yang, Wen-Hao ^{[1
]}

Huang, Chi-Hung ^{[3
]}

Kao, Shou-Yen ^{[7
]}

Tzeng, Cheng-Hwai ^{[3
]}

Tai, Shyh-Kuan ^{[8
]}

Chang, Shyue-Yih ^{[4
,8
]}

Lee, Oscar Kuang-Sheng ^{[1
,9
]}

Wu, Kou-Juey ^{[4
,6
,10
]}

机构：

[1] Natl Yang Ming Univ, Inst Clin Med, Taipei 112, Taiwan

[2] Natl Yang Ming Univ, Inst Biotechnol Med, Taipei 112, Taiwan

[3] Taipei Vet Gen Hosp, Dept Med, Div Hematol Oncol, Taipei 112, Taiwan

[4] Taipei Vet Gen Hosp, Genom Res Ctr, Taipei 112, Taiwan

[5] Inst Microbiol & Immunol, Taipei 112, Taiwan

[6] Taiwan Adv Biopharm Inc, Xizhi City 221, Taipei County, Taiwan

[7] Taipei Vet Gen Hosp, Dept Dent, Taipei 112, Taiwan

[8] Taipei Vet Gen Hosp, Dept Otolaryngol, Taipei 112, Taiwan

[9] Taipei Vet Gen Hosp, Dept Med Res & Educ, Taipei 112, Taiwan

[10] Natl Yang Ming Univ, Inst Biochem & Mol Biol, Taipei 112, Taiwan

来源：

NATURE CELL BIOLOGY | 2010年 / 12卷 / 10期

关键词：

CANCER STEM-CELLS; E-CADHERIN REPRESSION; NECK-CANCER; GENE-EXPRESSION; SELF-RENEWAL; METHYLTRANSFERASE ACTIVITY; IN-VIVO; KAPPA-B; HEAD; HYPOXIA;

D O I：

10.1038/ncb2099

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：982 / 992

页数：11

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