Bcl-3 promotes Wnt signaling by maintaining the acetylation of beta-catenin at lysine 49 in colorectal cancer
2020-05-01
发表期刊SIGNAL TRANSDUCTION AND TARGETED THERAPY (IF:40.8[JCR-2023],40.5[5-Year])
ISSN2095-9907
EISSN2059-3635
卷号5期号:1
发表状态已发表
DOI10.1038/s41392-020-0138-6
摘要Wnt/beta -catenin signaling plays a critical role in colorectal cancer (CRC) tumorigenesis and the homeostasis of colorectal cancer stem cells (CSCs), but its molecular mechanism remains unclear. B-cell lymphoma 3 (Bcl-3), a member of the I kappa B family, is overexpressed in CRC and promotes tumorigenicity. Here, we report a novel function of Bcl-3 in maintaining colorectal CSC homeostasis by activating Wnt/beta -catenin signaling. Silencing Bcl-3 suppresses the self-renewal capacity of colorectal CSCs and sensitizes CRC cells to chemotherapeutic drugs through a decrease in Wnt/beta -catenin signaling. Moreover, our data show that Bcl-3 is a crucial component of Wnt/beta -catenin signaling and is essential for beta -catenin transcriptional activity in CRC cells. Interestingly, Wnt3a increases the level and nuclear translocation of Bcl-3, which binds directly to beta -catenin and enhances the acetylation of beta -catenin at lysine 49 (Ac-K49-beta -catenin) and transcriptional activity. Bcl-3 depletion decreases the Ac-K49-beta -catenin level by increasing the level of histone deacetylase 1 to remove acetyl groups from beta -catenin, thus interrupting Wnt/beta -catenin activity. In CRC clinical specimens, Bcl-3 expression negatively correlates with the overall survival of CRC patients. A significantly positive correlation was found between the expression of Bcl-3 and Ac-K49-beta -catenin. Collectively, our data reveal that Bcl-3 plays a crucial role in CRC chemoresistance and colorectal CSC maintenance via its modulation of the Ac-K49-beta -catenin, which serves as a promising therapeutic target for CRC.
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收录类别SCI ; SCIE
语种英语
资助项目National Program on Key Research[2018YFA0107500][2016YFC1302400] ; National Basic Research Program[2014CB541904][2014CB943600] ; National Natural Science Foundation of China[91742113][31570902][81702950][81772798][91949102][81771752] ; Natural Science Foundation of Shanghai[14ZR1426300][18ZR1424400][18ZR1446400][18431902700] ; China Postdoctoral Science Foundation[2017M611633]
WOS研究方向Biochemistry & Molecular Biology ; Cell Biology
WOS类目Biochemistry & Molecular Biology ; Cell Biology
WOS记录号WOS:000531321800001
出版者NATURE PUBLISHING GROUP
WOS关键词STEM-CELLS ; TUMORIGENESIS ; ACTIVATION ; EXPRESSION ; BINDING ; TARGET ; PHOSPHORYLATION ; DIFFERENTIATION ; PROLIFERATION ; TRANSCRIPTION
原始文献类型Article
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文献类型期刊论文
条目标识符https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/120870
专题免疫化学研究所_特聘教授组_干细胞生物学实验室
通讯作者Wang, Mingliang; Liu, Sanhong; Zhang, Xiaoren
作者单位
1.Chinese Acad Sci, Univ Chinese Acad Sci, CAS Key Lab Tissue Microenvironm & Tumor, Shanghai Inst Biol Sci,Shanghai Inst Nutr & Hlth, Shanghai 200025, Peoples R China
2.ShanghaiTech Univ, Shanghai Inst Adv Immunochem Studies, Shanghai 201210, Peoples R China
3.Guangzhou Med Univ, Guangzhou Municipal & Guangdong Prov Key Lab Prot, State Key Lab Resp Dis, Affiliated Canc Hosp & Inst, Guangzhou 510000, Peoples R China
4.Shanghai Jiao Tong Univ, Renji Hosp, Sch Med, Shanghai 200025, Peoples R China
5.Shanghai Jiao Tong Univ, Renji Hosp, Shanghai Canc Inst, State Key Lab Oncogenes & Related Genes,Sch Med, Shanghai 200032, Peoples R China
6.Shanghai Jiao Tong Univ, Ruijin Hosp, Dept Gen Surg, Sch Med, Shanghai 200025, Peoples R China
通讯作者单位免疫化学研究所
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Chen, Xi,Wang, Chen,Jiang, Yuhang,et al. Bcl-3 promotes Wnt signaling by maintaining the acetylation of beta-catenin at lysine 49 in colorectal cancer[J]. SIGNAL TRANSDUCTION AND TARGETED THERAPY,2020,5(1).
APA Chen, Xi.,Wang, Chen.,Jiang, Yuhang.,Wang, Qi.,Tao, Yu.,...&Zhang, Xiaoren.(2020).Bcl-3 promotes Wnt signaling by maintaining the acetylation of beta-catenin at lysine 49 in colorectal cancer.SIGNAL TRANSDUCTION AND TARGETED THERAPY,5(1).
MLA Chen, Xi,et al."Bcl-3 promotes Wnt signaling by maintaining the acetylation of beta-catenin at lysine 49 in colorectal cancer".SIGNAL TRANSDUCTION AND TARGETED THERAPY 5.1(2020).
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