國家衛生研究院 NHRI:Item 3990099045/3093
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    题名: Axl promotes cell invasion by inducing MMP-9 activity through activation of NF-kappa B and Brg-1
    作者: Tai, KY;Shieh, YS;Lee, CS;Shiah, SG;Wu, CW
    贡献者: National Institute of Cancer Research
    摘要: Activity of the Axl receptor tyrosine kinase is positively correlated with tumor metastasis; however, its detailed role in the mechanism of tumor invasion is still not completely understood. Here, we show that Axl enhances the expression of matrix metalloproteinase 9 ( MMP-9), required for Axl-mediated invasion both in vitro and in vivo. We found that the highly selective MEK1/2 inhibitors U0126 and PD98059, and the expressed dominant-negative form of extracellular signal-regulated kinase ( ERK), completely block Axl-mediated MMP-9 activation. In contrast, the phosphatidylinositol 3-kinase inhibitor LY294002 and wortmannin had little effect on activation. Interestingly, however, the Axl ligand Gas6 is not involved in Axl-mediated MMP-9 activation. Mutation of Glu59(Axl) and Thr77(Axl) dramatically reduced Gas6-Axl binding but continued to induce MMP-9 activation. In addition, overexpression of Axl-activated ERK and enhanced nuclear factor-kappa B (NF-kappa B) transactivation and brahma-related gene-1 ( Brg-1) translocation. Exposure to the NF-kappa B inhibitor silibinin, which inhibits I kappa B alpha kinase activity, or overexpression of the dominant-negative mutant I kappa B and Brg-1 strikingly inhibited Axl-mediated MMP-9 activation. These data indicate that coordination of ERK signaling and NF-kappa B and Brg-1 activation are indispensable to regulation of Axl-dependent MMP-9 gene transcription. Together with previous data, our results provide a plausible mechanism for Axl-mediated tumor invasion and establish a functional link between the Axl and MMP-9 signaling pathways.
    关键词: Biochemistry & Molecular Biology;Oncology;Cell Biology;Genetics & Heredity
    日期: 2008-07-03
    關聯: Oncogene. 2008 Jul;27(29):4044-4055.
    Link to: http://dx.doi.org/10.1038/onc.2008.57
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0950-9232&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000257325100004
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=46449096930
    显示于类别:[吳成文(1996-2008)] 期刊論文
    [夏興國] 期刊論文

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