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Oncogene ; 38(7): 980-997, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30185813

RESUMO

Overexpression of Jumonji domain-containing 6 (JMJD6) has been reported to be associated with more aggressive breast cancer characteristics. However, the precise role of JMJD6 in breast cancer development remains unclear. Here, we demonstrate that JMJD6 has intrinsic tyrosine kinase activity and can utilize ATP and GTP as phosphate donors to phosphorylate Y39 of histone H2A.X (H2A.XY39ph). High JMJD6 levels promoted autophagy in triple negative breast cancer (TNBC) cells by regulating the expression of autophagy-related genes. The JMJD6-H2A.XY39ph axis promoted TNBC cell growth via the autophagy pathway. We show that combined inhibition of JMJD6 kinase activity and autophagy efficiently decreases TNBC growth. Together, these findings suggest an effective strategy for TNBC treatment.


Assuntos
Autofagia , Histonas/metabolismo , Histona Desmetilases com o Domínio Jumonji/metabolismo , Proteínas de Neoplasias/metabolismo , Neoplasias de Mama Triplo Negativas/metabolismo , Animais , Feminino , Histonas/genética , Humanos , Histona Desmetilases com o Domínio Jumonji/genética , Camundongos , Camundongos Endogâmicos BALB C , Proteínas de Neoplasias/genética , Fosforilação , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologia
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