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Title:
Bmi1 is essential in Twist1-induced epithelial–mesenchymal transition | Nature Cell Biology
Description:
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.
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nature portfolio permissions reprints privacy policy twist1-induced epithelial–mesenchymal transition national research program advertising inhibiting c-myc-induced apoptosis ikk-nuclear factor-κb pathway social media cheng-hwai tzeng nature 425 nature 397 nature 428 nature 442 nature cancer research kou-juey wu shyue-yih chang muh-hwa yang repressing stemness-inhibiting micrornas national yang-ming university wen-hao yang shyh-kuan tai epithelial–mesenchymal transition o2-dependent degradation domain multi-lineage differentiation capacity drb sensitivity-inducing factor dennis shin-shian hsu neck cancer biology author correction hif-1α promotes metastasis mesenchymal transition maria hypoxia-inducible factor 1alpha polycomb-group protein epithelial–mesenchymal transitions transcriptome reprogramming induced springerlink instant access drosophila mesoderm development permissions gene expression profiling neural stem cell shou-yen kao article yang genomic medicine grants personal data hsei-wei wang histone methyltransferase activity chi-hung huang squamous cell carcinoma twist1-induced emt
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name:Department of Otolaryngology, Taipei Veterans General Hospital, Taiwan
type:PostalAddress
type:Organization
name:Oscar Kuang-Sheng Lee
affiliation:
name:Institute of Clinical Medicine, National Yang-Ming University
address:
name:Institute of Clinical Medicine, National Yang-Ming University, Peitou, Taiwan
type:PostalAddress
type:Organization
name:Taipei Veterans General Hospital
address:
name:Department of Medical Research & Education, Taipei Veterans General Hospital, Taiwan
type:PostalAddress
type:Organization
name:Kou-Juey Wu
affiliation:
name:Genomic Research Center, Taipei Veterans General Hospital
address:
name:Genomic Research Center, Taipei Veterans General Hospital, Taiwan
type:PostalAddress
type:Organization
name:Institute of Biochemistry & Molecular Biology, National Yang-Ming University
address:
name:Institute of Biochemistry & Molecular Biology, National Yang-Ming University, Peitou District, Taiwan
type:PostalAddress
type:Organization
email:[email protected]
PostalAddress:
name:Institute of Clinical Medicine, National Yang-Ming University, Peitou, Taiwan
name:Institute of Biotechnology in Medicine, National Yang-Ming University, Peitou, Taiwan
name:Division of Hematology-Oncology, Department of Medicine, Taipei Veterans General Hospital, Taiwan
name:Genomic Research Center, Taipei Veterans General Hospital, Taiwan
name:Institute of Clinical Medicine, National Yang-Ming University, Peitou, Taiwan
name:Institute of Clinical Medicine, National Yang-Ming University, Peitou, Taiwan
name:Genomic Research Center, Taipei Veterans General Hospital, Taiwan
name:Institute of Microbiology & Immunology, Peitou, Taiwan
name:Institute of Clinical Medicine, National Yang-Ming University, Peitou, Taiwan
name:Institute of Clinical Medicine, National Yang-Ming University, Peitou, Taiwan
name:Institute of Clinical Medicine, National Yang-Ming University, Peitou, Taiwan
name:Taiwan Advance Biopharm, Inc, Xizhi City, Taiwan
name:Department of Dentistry, Taipei Veterans General Hospital, Taiwan
name:Division of Hematology-Oncology, Department of Medicine, Taipei Veterans General Hospital, Taiwan
name:Department of Otolaryngology, Taipei Veterans General Hospital, Taiwan
name:Genomic Research Center, Taipei Veterans General Hospital, Taiwan
name:Department of Otolaryngology, Taipei Veterans General Hospital, Taiwan
name:Institute of Clinical Medicine, National Yang-Ming University, Peitou, Taiwan
name:Department of Medical Research & Education, Taipei Veterans General Hospital, Taiwan
name:Genomic Research Center, Taipei Veterans General Hospital, Taiwan
name:Institute of Biochemistry & Molecular Biology, National Yang-Ming University, Peitou District, Taiwan
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