NatD epigenetically activates FOXA2 expression to promote breast cancer progression by facilitating MMP14 expression
Mengying Xing,
Bing Yao,
Jiaxuan Xu,
Peifen Lu,
Qixiang Li,
Dongliang Wu,
Bing Chen,
Jiwu Wei,
Lei Su,
Quan Zhao
Affiliations
Mengying Xing
The State Key Laboratory of Pharmaceutical Biotechnology, Department of Hematology and General Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, China-Australia Institute of Translational Medicine, School of Life Sciences, Nanjing University, Nanjing 210046, China
Bing Yao
National Experimental Teaching Center of Basic Medical Science, Nanjing Medical University, Nanjing, China
Jiaxuan Xu
The State Key Laboratory of Pharmaceutical Biotechnology, Department of Hematology and General Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, China-Australia Institute of Translational Medicine, School of Life Sciences, Nanjing University, Nanjing 210046, China
Peifen Lu
The State Key Laboratory of Pharmaceutical Biotechnology, Department of Hematology and General Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, China-Australia Institute of Translational Medicine, School of Life Sciences, Nanjing University, Nanjing 210046, China
Qixiang Li
The State Key Laboratory of Pharmaceutical Biotechnology, Department of Hematology and General Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, China-Australia Institute of Translational Medicine, School of Life Sciences, Nanjing University, Nanjing 210046, China
Dongliang Wu
The State Key Laboratory of Pharmaceutical Biotechnology, Department of Hematology and General Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, China-Australia Institute of Translational Medicine, School of Life Sciences, Nanjing University, Nanjing 210046, China
Bing Chen
The State Key Laboratory of Pharmaceutical Biotechnology, Department of Hematology and General Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, China-Australia Institute of Translational Medicine, School of Life Sciences, Nanjing University, Nanjing 210046, China
Jiwu Wei
Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, Nanjing, China; Corresponding author
Lei Su
The State Key Laboratory of Pharmaceutical Biotechnology, Department of Hematology and General Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, China-Australia Institute of Translational Medicine, School of Life Sciences, Nanjing University, Nanjing 210046, China; Corresponding author
Quan Zhao
The State Key Laboratory of Pharmaceutical Biotechnology, Department of Hematology and General Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, China-Australia Institute of Translational Medicine, School of Life Sciences, Nanjing University, Nanjing 210046, China; Corresponding author
Summary: N-α-acetyltransferase D (NatD) mediates N-α-terminal acetylation of histone H4 (Nt-Ac-H4), but its role in breast cancer metastasis remains unknown. Here, we show that depletion of NatD directly represses the expression of FOXA2, and is accompanied by a significant reduction in Nt-Ac-H4 enrichment at the FOXA2 promoter. We show that NatD is commonly upregulated in primary breast cancer tissues, where its expression level correlates with FOXA2 expression, enhanced invasiveness, and poor clinical outcomes. Furthermore, we show that FOXA2 promotes the migration and invasion of breast cancer cells by activating MMP14 expression. MMP14 is also upregulated in breast cancer tissues, where its expression level correlates with FOXA2 expression and poor clinical prognosis. Our study shows that the NatD-FOXA2-MMP14 axis functions as a key signaling pathway to promote the migratory and invasive capabilities of breast cancer cells, suggesting that NatD is a critical epigenetic modulator of cell invasion during breast cancer progression.
