國家衛生研究院 NHRI:Item 3990099045/9645
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    题名: Docosahexaenoic acid inhibits 12-O-tetradecanoylphorbol-13- acetate-induced fascin-1-dependent breast cancer cell migration by suppressing the PKCdelta- and Wnt-1/beta-catenin-mediated pathways
    其它题名: Docosahexaenoic acid inhibits 12-O-tetradecanoylphorbol-13- acetate-induced fascin-1-dependent breast cancer cell migration by suppressing the PKCδ- and Wnt-1/β-catenin-mediated pathways
    作者: Lii, CK;Chang, JW;Chen, JJ;Chen, HW;Liu, KL;Yeh, SL;Wang, TS;Liu, SH;Tsai, CH;Li, CC
    贡献者: Institute of Molecular and Genomic Medicine
    摘要: Fascin-1, an actin-bundling protein, plays an important role in cancer cell migration and invasion; however, the underlying mechanism remains unclear. On the basis of a 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced cell migration model, it was shown that TPA increased fascin-1 mRNA and protein expression and fascin-1-dependent cell migration. TPA dose- and time-dependently increased PKCdelta and STAT3alpha activation and GSK3beta phosphorylation; up-regulated Wnt-1, beta-catenin, and STAT3alpha expression; and increased the nuclear translocation of beta-catenin and STAT3alpha. Rottlerin, a PKCdelta inhibitor, abrogated the increases in STAT3alpha activation and beta-catenin and fascin-1 expression. WP1066, a STAT3 inhibitor, suppressed TPA-induced STAT3alpha DNA binding activity and beta-catenin expression. Knockdown of beta-catenin attenuated TPA-induced fascin-1 and STAT3alpha expression as well as cell migration. In addition to MCF-7, migration of Hs578T breast cancer cells was inhibited by silencing fascin-1, beta-catenin, and STAT3alpha expression as well. TPA also induced Wnt-1 expression and secretion, and blocking Wnt-1 signaling abrogated beta-catenin induction. DHA pretreatment attenuated TPA-induced cell migration, PKCdelta and STAT3alpha activation, GSK3beta phosphorylation, and Wnt-1, beta-catenin, STAT3alpha, and fascin-1 expression. Our results demonstrated that TPA-induced migration is likely associated with the PKCdelta and Wnt-1 pathways, which lead to STAT3alpha activation, GSK3beta inactivation, and beta-catenin increase and up-regulation of fascin-1 expression. Moreover, the anti-metastatic potential of DHA is partly attributed to its suppression of TPA-activated PKCdelta and Wnt-1 signaling.
    日期: 2016-05
    關聯: Oncotarget. 2016 May;7(18):25162-25179.
    Link to: http://dx.doi.org/10.18632/oncotarget.7301
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000377722300019
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84967017012
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