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

Oncogene volume 38, pages 980–997 (2019)Cite this article

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Abstract

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.

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Data availability

Values for significantly differentially expressed genes are provided in Supplementary Table 2. Chip-sequence analyses are presented in Supplementary Tables 3. The raw data have been deposited in the ArrayExpress database at EMBL-EBI (http://www.ebi.ac.uk/arrayexpress) under accession number E-MTAB-6517 and E-MTAB-6539. All other data and reagents are available from the corresponding author upon reasonable request.

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Acknowledgements

This work was primarily supported by the National Natural Science Foundation of China (grant numbers 81772834, 81302324, 81301779). Other support include: Science Fund for Distinguished Young Scholars of North China University of Science and Technology (JQ201704); Doctoral Research Project of North China University of Science and Technology. This work was also supported by the Scientific Research Matching Funds of North China University of Science and Technology and scientific research funds of Tangshan People’s Hospital.

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  1. These authors contributed equally: Yan Liu, Yue-Hong Long, Shu-Qing Wang

Authors and Affiliations

  1. College of Life Science, North China University of Science and Technology, Tangshan, China

    Yan Liu, Yue-Hong Long & Yuan-Yue Zhang

  2. Cancer Institute, Tangshan People’s Hospital, Tangshan, China

    Yan Liu, Yuan-Yue Zhang, Yu-Feng Li & Jing-Hua Zhang

  3. Hospital of North China University of Science and Technology, Tangshan, China

    Shu-Qing Wang

  4. People’s Hospital of Zunhua, Zunhua, China

    Jiang-Sheng Mi, Cheng-Hua Yu, De-Yan Li & Xiao-Jun Zhang

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Correspondence to Shu-Qing Wang, Jing-Hua Zhang or Xiao-Jun Zhang.

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Liu, Y., Long, YH., Wang, SQ. et al. JMJD6 regulates histone H2A.X phosphorylation and promotes autophagy in triple-negative breast cancer cells via a novel tyrosine kinase activity. Oncogene 38, 980–997 (2019). https://doi.org/10.1038/s41388-018-0466-y

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