β-catenin deacetylation is essential for WNT‑induced proliferation of breast cancer cells

Wang,Shao-Hua; Li,Ning; Wei,Yao; Li,Qiu-Rong; Yu,Ze-Ping

doi:10.3892/mmr.2014.1889

β-catenin deacetylation is essential for WNT‑induced proliferation of breast cancer cells

Authors:
- Shao-Hua Wang
- Ning Li
- Yao Wei
- Qiu-Rong Li
- Ze-Ping Yu
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Affiliations: Department of General Surgery, Jinling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu 210002, P.R. China
Published online on: January 8, 2014 https://doi.org/10.3892/mmr.2014.1889
Pages: 973-978

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Abstract

Deregulation of the WNT signaling pathway is associated with the development and progression of breast cancer. β-catenin mutations have been found to constitutively activate β-catenin-T-cell factor (TCF) signaling in other types of cancer. β-catenin acetylation regulates β-catenin-TCF4 interaction in WNT signaling, but it remains unknown whether the acetylation of β-catenin is involved in WNT-induced proliferation of breast cancer cells. In this study, a lower level of acetylated β-catenin (K345) was observed in breast cancer tissues. WNT3A stimulated the downregulation of β-catenin acetylation and promoted the proliferation of MCF7 cells. The K345Q mutation in β-catenin inhibited WNT-induced cell growth and axin2/TCF7 upregulation in breast cancer cells. By contrast, K345R mutants could mimic deacetylated β-catenin to generate the WNT-elicited phenotype. Additionally, the acetylation of β-catenin may prime β-catenin for phosphorylation. Further investigation revealed that the deacetylase HDAC6 was responsible for WNT-induced deacetylation of β-catenin in breast cancer cells. In conclusion, the epigenetic modification of β-catenin may be essential for WNT signaling in breast cancer progression, and blocking the occurrence of β-catenin acetylation may provide a novel therapeutic approach for breast cancer.

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