NatD promotes lung cancer progression by preventing histone H4 serine phosphorylation to activate Slug expression

Junyi Ju, Aiping Chen, Yexuan Deng, Ming Liu, Ying Wang, Yadong Wang, Min Nie, Chao Wang, Hong Ding, Bing Yao, Tao Gui, Xinyu Li, Zhen Xu, Chi Ma, Yong Song, Marc Kvansakul, Ke Zen, Chen-Yu Zhang, Cheng Luo, Ming Fang, David C. S. Huang, C. David Allis, Renxiang Tan, Changjiang Kathy Zeng (), Jiwu Wei () and Quan Zhao ()
Additional contact information
Junyi Ju: Nanjing University
Aiping Chen: Nanjing University
Yexuan Deng: Nanjing University
Ming Liu: Nanjing University
Ying Wang: Nanjing University
Yadong Wang: Nanjing University
Min Nie: Nanjing University
Chao Wang: Southeast University
Hong Ding: Chinese Academy of Sciences
Bing Yao: Nanjing University
Tao Gui: Nanjing University
Xinyu Li: Nanjing University
Zhen Xu: University of Melbourne
Chi Ma: Nanjing University
Yong Song: Nanjing University
Marc Kvansakul: La Trobe University
Ke Zen: Nanjing University
Chen-Yu Zhang: Nanjing University
Cheng Luo: Chinese Academy of Sciences
Ming Fang: Southeast University
David C. S. Huang: University of Melbourne
C. David Allis: The Rockefeller University
Renxiang Tan: Nanjing University
Changjiang Kathy Zeng: SQJ Biotechnologies Limited
Jiwu Wei: Nanjing University
Quan Zhao: Nanjing University

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

Abstract: Abstract N-α-acetyltransferase D (NatD) mediates N-α-terminal acetylation (Nt-acetylation) of histone H4 known to be involved in cell growth. Here we report that NatD promotes the migratory and invasive capabilities of lung cancer cells in vitro and in vivo. Depletion of NatD suppresses the epithelial-to-mesenchymal transition (EMT) of lung cancer cells by directly repressing the expression of transcription factor Slug, a key regulator of EMT. We found that Nt-acetylation of histone H4 antagonizes histone H4 serine 1 phosphorylation (H4S1ph), and that downregulation of Nt-acetylation of histone H4 facilitates CK2α binding to histone H4 in lung cancer cells, resulting in increased H4S1ph and epigenetic reprogramming to suppress Slug transcription to inhibit EMT. Importantly, NatD is commonly upregulated in primary human lung cancer tissues where its expression level correlates with Slug expression, enhanced invasiveness, and poor clinical outcomes. These findings indicate that NatD is a crucial epigenetic modulator of cell invasion during lung cancer progression.

Date: 2017
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DOI: 10.1038/s41467-017-00988-5

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