NKX6.1 functions as a metastatic suppressor through epigenetic regulation of the epithelial–mesenchymal transition
Autor: | Chang Cp, Hsiao Th, Yu Pn, Su Hy, Huang Ky, Ya-Wen Lin, Hsin-Jung Li, Mu-Hsien Yu |
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Rok vydání: | 2015 |
Předmět: |
0301 basic medicine
Cancer Research Epithelial-Mesenchymal Transition animal structures Vimentin medicine.disease_cause Epigenesis Genetic Mice 03 medical and health sciences 0302 clinical medicine Cell Line Tumor Coactivator Genetics medicine Animals Humans Genes Tumor Suppressor Neoplasm Invasiveness Metastasis suppressor RNA Messenger Epithelial–mesenchymal transition Molecular Biology Transcription factor Homeodomain Proteins biology DNA Methylation Cadherins Molecular biology Gene Expression Regulation Neoplastic 030104 developmental biology 030220 oncology & carcinogenesis embryonic structures DNA methylation biology.protein Cancer research Original Article Retinoblastoma-Binding Protein 7 Carcinogenesis Corepressor Transcription Factors |
Zdroj: | Oncogene |
ISSN: | 1476-5594 0950-9232 |
Popis: | The transcription factor NKX6.1 (NK6 homeobox 1) is important in the development of pancreatic β-cells and neurons. Although recent publications show that NKX6.1 is hypermethylated and downregulated during tumorigenesis, the function of NKX6.1 in carcinogenesis remains elusive. Here, we address the metastasis suppressor function of human NKX6.1 using cell, animal and clinical analyses. Our data show that NKX6.1 represses tumor formation and metastatic ability both in vitro and in vivo. Mechanistically, NKX6.1 suppresses cell invasion by inhibiting the epithelial-to-mesenchymal transition (EMT). NKX6.1 directly enhances the mRNA level of E-cadherin by recruiting BAF155 coactivator and represses that of vimentin and N-cadherin by recruiting RBBP7 (retinoblastoma binding protein 7) corepressor. Clinical cancer tumors with metastasis show low NKX6.1 protein expression coinciding with low E-cadherin and high vimentin expression. Our results demonstrate that NKX6.1 functions as an EMT suppressor by interacting with different epigenetic modifiers, making it a potential novel therapeutic option. |
Databáze: | OpenAIRE |
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