GATA3 recruits UTX for gene transcriptional activation to suppress metastasis of breast cancer.
Cell Death Dis
; 10(11): 832, 2019 11 04.
Article
em En
| MEDLINE
| ID: mdl-31685800
ABSTRACT
GATA3 has emerged as a prominent transcription factor required for maintaining mammary-gland homeostasis. GATA3 loss is associated with aggressive breast cancer development, but the mechanism by which breast cancer is affected by the loss of GATA3 function remains unclear. Here, we report that GATA3 expression is positively correlated with the expression of UTX, a histone H3K27 demethylase contained in the MLL4 methyltransferase complex, and that GATA3 recruits the chromatin-remodeling MLL4 complex and interacts directly with UTX, ASH2L, and RBBP5. Using RNA sequencing and chromatin immunoprecipitation and sequencing, we demonstrate that the GATA3/UTX complex synergistically regulates a cohort of genes including Dicer and UTX, which are critically involved in the epithelial-to-mesenchymal transition (EMT). Our results further show that the GATA3-UTX-Dicer axis inhibits EMT, invasion, and metastasis of breast cancer cells in vitro and the dissemination of breast cancer in vivo. Our study implicates the GATA3-UTX-Dicer axis in breast cancer metastasis and provides new mechanistic insights into the pathophysiological function of GATA3.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Mama
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Regulação Enzimológica da Expressão Gênica
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Regulação Neoplásica da Expressão Gênica
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Ativação Transcricional
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Fator de Transcrição GATA3
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Histona Desmetilases
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Proteínas de Neoplasias
Limite:
Female
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Humans
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article