Journal
SCIENCE CHINA-LIFE SCIENCES
Volume 64, Issue 4, Pages 563-574Publisher
SCIENCE PRESS
DOI: 10.1007/s11427-020-1736-5
Keywords
Slug; acetylation; breast cancer; EMT
Categories
Funding
- Ministry of Science and Technology of the People's Republic of China [2016YFC1302103]
- National Natural Science Foundation of China [81621063, 81730071, 81972616, 81670626]
- Natural Science Foundation of Beijing Municipality [7171005]
- Peking University Medical Sciences Grant [BMU 2018JC004]
- Beijing Natural Science Foundation [7202080]
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In breast cancer cells, acetylation by CBP increases the stability of Slug, promoting epithelial to mesenchymal transition (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 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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