DAX1 promotes cervical cancer cell growth and tumorigenicity through activation of Wnt/β-catenin pathway via GSK3β.
DAX1 promotes cervical cancer cell growth and tumorigenicity through activation of Wnt/β-catenin pathway via GSK3β.
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DAX1 通过 GSK3 beta 激活 Wnt/β-catenin 通路促进宫颈癌细胞生长和致瘤性
DOI：
10.1038/s41419-018-0359-6
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发表时间：
2018-03-01
影响因子：
9
通讯作者：
Yang WT
中科院分区：
文献类型：
--
作者：
Liu XF;Li XY;Zheng PS;Yang WT
DAX 1以其在几种类型的癌症中的基本作用而闻名，而其在宫颈癌中的生物学作用在很大程度上尚未探索。应用免疫组化和western blot检测宫颈癌组织中DAX 1的表达。还研究了DAX 1沉默对细胞生长、肿瘤形成和CSC（癌症干细胞）特性的影响。DAX 1的表达从正常宫颈到高度鳞状上皮内病变逐渐增加，并因此增加到宫颈癌。DAX 1的沉默显著抑制细胞生长、致瘤性和肿瘤球形成。TOP/FOP-Flash报告基因检测结果显示，DAX 1沉默的宫颈癌细胞中Wnt/β-catenin通路被显著灭活，Wnt/β-catenin靶向基因cyclinD 1和c-myc表达下调。此外，双荧光素酶报告基因和染色质免疫沉淀（ChIP）分析证实，DAX 1通过与糖原合成酶激酶3β（GSK 3 β）启动子上的−666~−444基序物理相互作用，转录抑制GSK 3β（Wnt/β-catenin途径的抑制剂）。此外，通过CHIR-99021阻断GSK 3 β导致由DAX 1沉默诱导的CSC特征显著增加。DAX 1在宫颈癌中过表达，并通过激活GSK 3 β介导的Wnt/β-catenin通路促进细胞生长和致瘤性。
DAX1 is well known for its fundamental role in several types of cancer, while its biological role in cervical cancer remains largely unexplored. The expression of DAX1 in cervical carcinoma tissue was examined using immunohistochemistry and western blot. The effects of DAX1 silencing on the cell growth, tumor formation, and CSC (cancer stem cell) characteristics were also investigated. DAX1 expressed a gradual increase from normal cervix to high-grade squamous intraepithelial lesions, and consequently to cervical cancer. Silence of DAX1 significantly inhibited the cell growth, tumorigenicity, and tumorsphere formation. Furthermore, the TOP/FOP-Flash reporter assay revealed that Wnt/β-catenin pathway was significantly inactivated in DAX1-silenced cervical cancer cells with the downregulation of Wnt/β-catenin targeting genes, including cyclinD1 and c-myc. Moreover, dual-luciferase reporter and chromatin immunoprecipitation (ChIP) assay confirmed that DAX1 transcriptionally repressed glycogen synthase kinase 3β (GSK3β), an inhibitor of the Wnt/β-catenin pathway, by physically interacting with −666~−444 motif on the GSK3β promoter. Additionally, the blockage of GSK3β by CHIR-99021 resulted in a significant increase of CSC characteristics induced by the silence of DAX1. Our data demonstrated that DAX1 is overexpressed in cervical cancer, and that it promotes cell growth and tumorigenicity through activating Wnt/β-catenin pathway mediated by GSK3β.
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影响因子：
254.7
作者：
Siegel, Rebecca;Ma, Jiemin;Jemal, Ahmedin
通讯作者：
Jemal, Ahmedin
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影响因子：
--
作者：
Chen Q;Zheng PS;Yang WT
通讯作者：
Yang WT
影响因子：
3.5
作者：
Martins, Rute S. T.;Power, Deborah M.;Canario, Adelino V. M.
通讯作者：
Canario, Adelino V. M.
影响因子：
4.1
作者：
McCabe, Edward R. B.
通讯作者：
McCabe, Edward R. B.
影响因子：
3.1
作者：
Zhao, Huajun;Li, Zili;Lan, Zi-Jian
通讯作者：
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