SOX17 restrains proliferation and tumor formation by down-regulating activity of the Wnt/β-catenin signaling pathway via trans-suppressing β-catenin in cervical cancer.
SOX17 restrains proliferation and tumor formation by down-regulating activity of the Wnt/β-catenin signaling pathway via trans-suppressing β-catenin in cervical cancer.
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SOX17 通过反式抑制 ss-catenin 下调宫颈癌中 Wnt/ss-catenin 信号通路的活性，从而抑制增殖和肿瘤形成
DOI：
10.1038/s41419-018-0782-8
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发表时间：
2018-07-03
影响因子：
9
通讯作者：
Liu XF
中科院分区：
文献类型：
--
作者：
Li L;Yang WT;Zheng PS;Liu XF
SRY-box基因17（SOX 17）被认为是干细胞维持的调节因子，在某些恶性肿瘤中是抑制因子。然而，SOX 17在宫颈癌发生发展过程中的生物学功能和分子机制尚不清楚。在本研究中，免疫组化显示SOX 17在正常宫颈中高表达，在高度鳞状上皮内病变中中等表达，在宫颈癌中低表达。SOX 17在体外抑制宫颈癌细胞的增殖和活力，以及在体内抑制肿瘤形成。另外，SOX 17诱导细胞周期停滞在从G 0/G1期到S期的转变。TOP/ FOP-Flash报告基因检测和Western blotting结果显示，SOX 17抑制了宫颈癌Wnt/β-catenin信号通路的活性。此外，萤火虫荧光素酶报告基因测定和定量染色质免疫沉淀（qChIP）测定证实，SOX 17通过直接结合β-catenin启动子的特定区域来反式抑制β-catenin的表达。总之，我们的数据表明，SOX 17通过反式抑制β-catenin来下调Wnt/β-catenin信号通路的活性，从而抑制宫颈癌的增殖和肿瘤形成。
The SRY-box containing gene 17 (SOX17) is considered as a regulator in stemness maintenance and a suppressor in some malignant tumors. However, the biological function and molecular mechanism of SOX17 in the process of initiation and progression of cervical cancer remain obscure. In this study, immunohistochemistry showed that the expression of SOX17 was high in the normal cervix, moderate in the high-grade squamous intraepithelial lesion, and low in the cervical cancer. SOX17 inhibited the proliferation and viability of cervical cancer cells in vitro as well as tumor formation in vivo. Additionally, SOX17 induced the cell cycle arrest at the transition from the G0/G1 phase to the S phase. The TOP/ FOP-Flash reporter assay and Western blotting showed SOX17 inhibited the activity of the Wnt/β-catenin signaling pathway in cervical cancer. Further, firefly luciferase reporter assay and quantitative chromatin immunoprecipitation (qChIP) assays confirmed that SOX17 trans-suppressed the expression of β-catenin by directly binding to the specific region of the β-catenin promoter. Together, our data demonstrated that SOX17 restrained the proliferation and tumor formation by down-regulating the activity of the Wnt/β-catenin signaling pathway via trans-suppression of β-catenin in cervical cancer.
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影响因子：
3.3
作者：
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通讯作者：
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影响因子：
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通讯作者：
Crawford HC
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6.4
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