國家衛生研究院 NHRI:Item 3990099045/10183
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    题名: Epigenetic switch between SOX2 and SOX9 regulates cancer cell plasticity
    作者: Lin, SC;Chou, YT;Jiang, SS;Chang, JL;Chung, CH;Kao, YR;Chang, IS;Wu, CW
    贡献者: National Institute of Cancer Research
    摘要: Cell differentiation within stem cell lineages can check proliferative potential, but nodal pathways that can limit tumor growth are obscure. Here, we report that lung cancer cell populations generate phenotypic and oncogenic plasticity via a switch between differentiation programs controlled by SOX2 and SOX9, thus altering proliferative and invasive capabilities. In lung cancer cells, SOX2 bound the EPCAM promoter to induce EpCAM-p21Cip1 - cyclin A2 signaling, encouraging cell proliferation as well as barrier properties. In contrast, SOX9 bound the SLUG promoter to induce SLUG-mediated cell invasion with a spindle-like phenotype. Pharmacologic inhibition of HDAC elevated a SOX9-positive cell population from SOX2-positive cells, whereas ectopic expression of SOX2 inhibited SOX9 with increased H3K9me2 levels on the SOX9 promoter. In clinical specimens, the expression of SOX2 and SOX9 correlated negatively and positively with lung tumor grade, respectively. Our findings identify SOX2 and SOX9 as nodal epigenetic regulators in determining cancer cell plasticity and metastatic progression.
    日期: 2016-12
    關聯: Cancer Research. 2016 Dec;76(23):7036-7048.
    Link to: http://dx.doi.org/10.1158/0008-5472.CAN-15-3178
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0008-5472&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000389435800027
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85002518543
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