title: β-catenin deacetylation is essential for WNT-induced proliferation of breast cancer cells.
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.
authors.affiliation: Department of General Surgery, Jinling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu 210002, P.R. China.
authors.forename: Shao-Hua
authors.initials: SH
authors.lastname: Wang
authors.affiliation: Department of General Surgery, Jinling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu 210002, P.R. China.
authors.forename: Ning
authors.initials: N
authors.lastname: Li
authors.affiliation: Department of General Surgery, Jinling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu 210002, P.R. China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Wei
authors.affiliation: Department of General Surgery, Jinling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu 210002, P.R. China.
authors.forename: Qiu-Rong
authors.initials: QR
authors.lastname: Li
authors.affiliation: Department of General Surgery, Jinling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu 210002, P.R. China.
authors.forename: Ze-Ping
authors.initials: ZP
authors.lastname: Yu
mesh_terms: D000107:Acetylation; D060466:Axin Protein / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism / Q000503:physiopathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015536:Down-Regulation; D005260:Female; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006801:Humans; D061986:MCF-7 Cells; D009154:Mutation; D010766:Phosphorylation; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D051822:T Cell Transcription Factor 1 / Q000378:metabolism; D015854:Up-Regulation; D060449:Wnt Signaling Pathway; D060509:Wnt3A Protein / Q000378:metabolism*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: C491761:AXIN2 protein, human; D060466:Axin Protein; D034741:RNA, Small Interfering; D051822:T Cell Transcription Factor 1; C497576:TCF7 protein, human; D060509:Wnt3A Protein; D051176:beta Catenin; C433811:HDAC6 protein, human; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases