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CBP-mediated Slug acetylation stabilizes Slug and promotes EMT and migration of breast cancer cells

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Abstract

Slug, a member of the Snail family of transcriptional repressors, plays a key role in cancer progression, cellular plasticity, and epithelial to mesenchymal transition (EMT). Slug is a fast-turnover protein and its stability is controlled by post-translational modifications. Here, we identified that Slug is acetylated by acetyltransferase CREB-binding protein (CBP) in breast cancer cells. CBP directly interacts with the C-terminal domain of Slug through its catalytic histone acetyltransferase (HAT) domain, leading to acetylation of Slug at lysines 166 and 211. Analysis with acetylation-specific antibodies revealed that Slug is highly acetylated in metastatic breast cancer cells. Notably, Slug acetylation, mediated by CBP at lysines 166 and 211, doubles its half-life and increases its stability. Further, acetylated Slug downregulates the expression of E-cadherin, the epithelial marker, and upregulates the expression of N-cadherin and vimentin, thereby promoting breast cancer cell migration. In conclusion, the present study demonstrates that CBP-mediated Slug acetylation increases its stability, promoting EMT and migration of breast cancer cells.

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Acknowledgements

This work was supported by grants from Ministry of Science and Technology of the People’s Republic of China (2016YFC1302103), National Natural Science Foundation of China (81621063, 81730071, 81972616 and 81670626), Natural Science Foundation of Beijing Municipality (7171005), Peking University Medical Sciences Grant (BMU 2018JC004), and the Beijing Natural Science Foundation (7202080).

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Authors and Affiliations

  1. Department of Human Anatomy, Histology, and Embryology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) and State Key Laboratory of Natural and Biomimetic Drugs, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191, China

    Xiaoyan Dai, Yanli Xin, Weizhi Xu, Xiaofan Wei & Hongquan Zhang

  2. Department of Pathology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191, China

    Xiaoyan Dai & Xinxia Tian

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  1. Xiaoyan Dai
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  2. Yanli Xin
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  3. Weizhi Xu
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  4. Xinxia Tian
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  5. Xiaofan Wei
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Correspondence to Xinxia Tian, Xiaofan Wei or Hongquan Zhang.

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Dai, X., Xin, Y., Xu, W. et al. CBP-mediated Slug acetylation stabilizes Slug and promotes EMT and migration of breast cancer cells. Sci. China Life Sci. 64, 563–574 (2021). https://doi.org/10.1007/s11427-020-1736-5

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