JMJD6 regulates histone H2A.X phosphorylation and promotes autophagy in triple-negative breast cancer cells via a novel tyrosine kinase activity

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...

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Bibliographic Details
Published in:Oncogene 2019-02, Vol.38 (7), p.980-997
Main Authors: Liu, Yan, Long, Yue-Hong, Wang, Shu-Qing, Zhang, Yuan-Yue, Li, Yu-Feng, Mi, Jiang-Sheng, Yu, Cheng-Hua, Li, De-Yan, Zhang, Jing-Hua, Zhang, Xiao-Jun
Format: Article
Language:English
Subjects:
13/1
13/109
13/44
13/51
14/19
14/28
38/39
38/61
38/77
631/337/458/1733
631/337/572
631/67/1347
631/67/395
631/80/39
64/60
82/80
Amino acids
Animals
Apoptosis
Autophagy
Breast cancer
Cancer cells
Care and treatment
Cell Biology
Development and progression
Female
Gene expression
Genetic aspects
Guanosine triphosphate
Health aspects
Histone H2A
Histones - genetics
Histones - metabolism
Human Genetics
Humans
Internal Medicine
Jumonji Domain-Containing Histone Demethylases - genetics
Jumonji Domain-Containing Histone Demethylases - metabolism
Kinases
Medicine
Medicine & Public Health
Mice
Mice, Inbred BALB C
Neoplasm Proteins - genetics
Neoplasm Proteins - metabolism
Oncology
Oxidoreductases
Phagocytosis
Phenols (Class of compounds)
Phosphates
Phosphorylation
Protein-tyrosine kinase
Triple negative breast cancer
Triple Negative Breast Neoplasms - genetics
Triple Negative Breast Neoplasms - metabolism
Triple Negative Breast Neoplasms - pathology
Tyrosine
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Summary: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.X Y39ph ). High JMJD6 levels promoted autophagy in triple negative breast cancer (TNBC) cells by regulating the expression of autophagy-related genes. The JMJD6-H2A.X Y39ph 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.
ISSN:0950-9232
1476-5594
DOI:10.1038/s41388-018-0466-y