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

Ya-fang Wang, Jie Zhang, Yi Su, Yan-yan Shen, Dong-xian Jiang, Ying-yong Hou, Mei-yu Geng (), Jian Ding () and Yi Chen ()
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Ya-fang Wang: 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

Nature Communications, 2017, vol. 8, issue 1, 1-14

Abstract: 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.

Date: 2017
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DOI: 10.1038/s41467-017-00350-9

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