國家衛生研究院 NHRI:Item 3990099045/7542
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    題名: Oxidative stress enhances Axl-mediated cell migration through an Akt1/Rac1-dependent mechanism
    作者: Huang, JS;Cho, CY;Hong, CC;Yan, MD;Hsieh, MC;Lay, JD;Lai, GM;Cheng, AL;Chuang, SE
    貢獻者: National Institute of Cancer Research
    摘要: Persistent oxidative stress is common in cancer cells due to abnormal generation of reactive oxygen species (ROS) and has been associated with malignant phenotypes, such as chemotherapy resistance and metastasis. Both overexpression of Axl and abnormal ROS elevation have been linked to cell transformation and increased cell migration. However, the relationship between Axl and ROS in malignant cells migration has not been previously evaluated. Using an in vitro human lung cancer model, we examined the redox state of lung adenocarcinoma cell lines of low metastatic (CL1-0) and high metastatic (CL1-5) potentials. Here we report that Axl activation elicits ROS accumulation through the oxidase-coupled small GTPase Rac1. We also observed that oxidative stress could activate Axl phosphorylation to synergistically enhance cell migration. Further, Axl-signaling activated by H2O2 treatment results in enhancement of cell migration via a PI3K/Akt-dependent pathway. The kinase activity of Axl is required for the Axl-mediated cell migration and prolongs the half-life of phospho-Akt under oxidative stress. Finally, down-regulation of Akt1, but not Akt2, by RNAi in Axl-overexpressing cells inhibits the amount of activated Rac-1 and the ability of migration induced by H2O2 treatment. Together, these results show that a novel Axl-signaling cascade induced by H2O2 treatment triggers cell migration through PI3K/AKT1/Rac1 pathway. Elucidation of redox regulation in the Axl-related malignant migration may provide new molecular insights into the mechanisms underlying tumor progression.
    日期: 2013-12
    關聯: Free Radical Biology and Medicine. 2013 Dec;65:1246-1256.
    Link to: http://dx.doi.org/10.1016/j.freeradbiomed.2013.09.011
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0891-5849&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000328868900118
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84885340255
    顯示於類別:[莊雙恩] 期刊論文
    [賴基銘(2004-2008)] 期刊論文

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