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    Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/8605


    Title: IKKbeta enforces a LIN28B/TCF7L2 positive feedback loop that promotes cancer cell stemness and metastasis
    Other Titles: IKKβ enforces a LIN28B/TCF7L2 positive feedback loop that promotes cancer cell stemness and metastasis
    Authors: Chen, C;Cao, FQ;Bai, LP;Liu, Y;Xie, JL;Wang, W;Si, Q;Yang, J;Chang, A;Liu, DH;Chuang, TH;Xiang, R;Luo, YP
    Contributors: Immunology Research Center
    Abstract: Considerable evidence suggests that pro-inflammatory pathways drive self-renewal of cancer stem-like cells (CSC), but the underlying mechanisms remain mainly undefined. Here we report that the let7 repressor LIN28B and its regulator IKKbeta sustain cancer cell stemness by interacting with the Wnt/TCF7L2 (TCF4) signaling pathway to promote cancer progression. We found that LIN28B expression correlated with clinical progression and stemness marker expression in breast cancer patients. Functional studies demonstrated that the stemness properties of LIN28B-expressing human breast and lung cancer cells were enhanced by IKKbeta, whereas loss of LIN28B abolished stemness properties in these settings. These phenomena were driven through interactions with TCF7L2, which enhanced LIN28B expression by direct binding to intron 1 of the LIN28B gene, which in turn promoted TCF7L2 mRNA translation through a positive feedback loop. Notably, RNAi-mediated silencing of LIN28B or pharmacological inhibition of IKKbeta was sufficient to suppress primary and metastatic tumor growth in vivo. Together, our results establish the LIN28B/TCF7L2 interaction loop as a central mediator of cancer stemness driven by pro-inflammatory processes during progression and metastasis, possibly offering a new therapeutic target for generalized interventions in advanced cancers.
    Date: 2015-04-15
    Relation: Cancer Research. 2015 Apr 15;75(8):1725-1735.
    Link to: http://dx.doi.org/10.1158/0008-5472.can-14-2111
    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:000352896900019
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84937151454
    Appears in Collections:[莊宗顯] 期刊論文

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