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G9a regulates breast cancer growth by modulating iron homeostasis through the repression of ferroxidase hephaestin

Author

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  • Ya-fang Wang

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Jie Zhang

    (Chinese Academy of Sciences)

  • Yi Su

    (Chinese Academy of Sciences)

  • Yan-yan Shen

    (Chinese Academy of Sciences)

  • Dong-xian Jiang

    (Fudan University)

  • Ying-yong Hou

    (Fudan University)

  • Mei-yu Geng

    (Chinese Academy of Sciences)

  • Jian Ding

    (Chinese Academy of Sciences)

  • Yi Chen

    (Chinese Academy of Sciences)

Abstract

G9a, a H3K9 methyltransferase, shows elevated expression in many types of human cancers, particularly breast cancer. However, the tumorigenic mechanism of G9a is still far from clear. Here we report that G9a exerts its oncogenic function in breast cancer by repressing hephaestin and destruction cellular iron homeostasis. In the case of pharmacological inhibition or short hairpin RNA interference-mediated suppression of G9a, the expression and activity of hephaestin increases, leading to the observed decrease of intracellular labile iron content and the disturbance of breast cancer cell growth in vitro and in vivo. We also provide evidence that G9a interacts with HDAC1 and YY1 to form a multi-molecular complex that contributes to hephaestin silencing. Furthermore, high G9a expression and low hephaestin expression correlate with poor survival of breast cancer are investigated. All these suggest a G9a-dependent epigenetic program in the control of iron homeostasis and tumor growth in breast cancer.

Suggested Citation

  • Ya-fang Wang & Jie Zhang & Yi Su & Yan-yan Shen & Dong-xian Jiang & Ying-yong Hou & Mei-yu Geng & Jian Ding & Yi Chen, 2017. "G9a regulates breast cancer growth by modulating iron homeostasis through the repression of ferroxidase hephaestin," Nature Communications, Nature, vol. 8(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-00350-9
    DOI: 10.1038/s41467-017-00350-9
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    Cited by:

    1. Xin-yu He & Xiao Fan & Lei Qu & Xiang Wang & Li Jiang & Ling-jie Sang & Cheng-yu Shi & Siyi Lin & Jie-cheng Yang & Zuo-zhen Yang & Kai Lei & Jun-hong Li & Huai-qiang Ju & Qingfeng Yan & Jian Liu & Fud, 2023. "LncRNA modulates Hippo-YAP signaling to reprogram iron metabolism," Nature Communications, Nature, vol. 14(1), pages 1-17, December.

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