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：
Chen, X;Cheung, ST;Brown, PO
通讯作者：
Brown, PO
影响因子：
16.6
作者：
Banerjee, Rajat;Russo, Nickole;Liu, Min;Basrur, Venkatesha;Bellile, Emily;Palanisamy, Nallasivam;Scanlon, Christina S.;van Tubergen, Elizabeth;Inglehart, Ronald C.;Metwally, Tarek;Mani, Ram-Shankar;Yocum, Anastasia;Nyati, Mukesh K.;Castilho, Rogerio M.;Varambally, Sooryanarayana;Chinnaiyan, Arul M.;D'Silva, Nisha J.
通讯作者：
D'Silva, Nisha J.
影响因子：
29.4
作者：
Delgiorno KE;Hall JC;Takeuchi KK;Pan FC;Halbrook CJ;Washington MK;Olive KP;Spence JR;Sipos B;Wright CV;Wells JM;Crawford HC
通讯作者：
Crawford HC
影响因子：
64.5
作者：
Hudson, C;Clements, D;Woodland, HR
通讯作者：
Woodland, HR
影响因子：
64.8
作者：
Cancer Genome Atlas Research Network;Albert Einstein College of Medicine;Analytical Biological Services;Barretos Cancer Hospital;Baylor College of Medicine;Beckman Research Institute of City of Hope;Buck Institute for Research on Aging;Canada's Michael Smith Genome Sciences Centre;Harvard Medical School;Helen F. Graham Cancer Center &Research Institute at Christiana Care Health Services;HudsonAlpha Institute for Biotechnology;ILSbio, LLC;Indiana University School of Medicine;Institute of Human Virology;Institute for Systems Biology;International Genomics Consortium;Leidos Biomedical;Massachusetts General Hospital;McDonnell Genome Institute at Washington University;Medical College of Wisconsin;Medical University of South Carolina;Memorial Sloan Kettering Cancer Center;Montefiore Medical Center;NantOmics;National Cancer Institute;National Hospital, Abuja, Nigeria;National Human Genome Research Institute;National Institute of Environmental Health Sciences;National Institute on Deafness &Other Communication Disorders;Ontario Tumour Bank, London Health Sciences Centre;Ontario Tumour Bank, Ontario Institute for Cancer Research;Ontario Tumour Bank, The Ottawa Hospital;Oregon Health &Science University;Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center;SRA International;St Joseph's Candler Health System;Eli &Edythe L. Broad Institute of Massachusetts Institute of Technology &Harvard University;Research Institute at Nationwide Children's Hospital;Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University;University of Bergen;University of Texas MD Anderson Cancer Center;University of Abuja Teaching Hospital;University of Alabama at Birmingham;University of California, Irvine;University of California Santa Cruz;University of Kansas Medical Center;University of Lausanne;University of New Mexico Health Sciences Center;University of North Carolina at Chapel Hill;University of Oklahoma Health Sciences Center;University of Pittsburgh;University of São Paulo, Ribeir ão Preto Medical School;University of Southern California;University of Washington;University of Wisconsin School of Medicine &Public Health;Van Andel Research Institute;Washington University in St Louis
通讯作者：
Washington University in St Louis