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

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...

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Bibliographic Details
Published in:Science China. Life sciences 2021-04, Vol.64 (4), p.563-574
Main Authors: Dai, Xiaoyan, Xin, Yanli, Xu, Weizhi, Tian, Xinxia, Wei, Xiaofan, Zhang, Hongquan
Format: Article
Language:English
Subjects:
Acetylation
Biomedical and Life Sciences
Breast cancer
Cell migration
CREB-binding protein
Cyclic AMP response element-binding protein
E-cadherin
Histone acetyltransferase
Life Sciences
Mesenchyme
Metastases
N-Cadherin
Post-translation
Protein turnover
Repressors
Research Paper
Snail protein
Transcription factors
Vimentin
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Summary: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.
ISSN:1674-7305
1869-1889
DOI:10.1007/s11427-020-1736-5