JMJD6 regulates histone H2A.X phosphorylation and promotes autophagy in triple-negative breast cancer cells via a novel tyrosine kinase activity
| Autor: | Jing-Hua Zhang, De-Yan Li, Jiang-Sheng Mi, Shu-Qing Wang, Cheng-Hua Yu, Yufeng Li, Yuan-Yue Zhang, Xiao-Jun Zhang, Yue-Hong Long, Yan Liu |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Cancer Research Jumonji Domain-Containing Histone Demethylases GTP' Triple Negative Breast Neoplasms Biology Histones 03 medical and health sciences Mice 0302 clinical medicine Breast cancer Histone H2A Genetics medicine Autophagy Animals Humans Kinase activity Phosphorylation Molecular Biology Triple-negative breast cancer Mice Inbred BALB C medicine.disease Neoplasm Proteins 030104 developmental biology 030220 oncology & carcinogenesis Cancer research Female Tyrosine kinase |
| Zdroj: | Oncogene. 38(7) |
| ISSN: | 1476-5594 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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