國家衛生研究院 NHRI:Item 3990099045/7316
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    Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/7316


    Title: Overexpression of Lon contributes to survival and aggressive phenotype of cancer cells through mitochondrial complex I-mediated generation of reactive oxygen species
    Authors: Cheng, CW;Kuo, CY;Fan, CC;Fang, WC;Jiang, SS;Lo, YK;Wang, TY;Kao, MC;Lee, AY
    Contributors: National Institute of Cancer Research
    Abstract: Lon protease is a multifunction protein and operates in protein quality control and stress response pathways in mitochondria. Human Lon is upregulated under oxidative and hypoxic stresses that represent the stress phenotypes of cancer. However, little literature undertakes comprehensive and detailed investigations on the tumorigenic role of Lon. Overexpression of Lon promotes cell proliferation, apoptotic resistance to stresses, and transformation. Furthermore, Lon overexpression induces the production of mitochondrial reactive oxygen species (ROS) that result from Lon-mediated upregulation of NDUFS8, a mitochondrial Fe-S protein in complex I of electron transport chain. Increased level of mitochondrial ROS promotes cell proliferation, cell survival, cell migration, and epithelial-mesenchymal transition through mitogen-activated protein kinase (MAPK) and Ras-ERK activation. Overall, the present report for the first time demonstrates the role of Lon overexpression in tumorigenesis. Lon overexpression gives an apoptotic resistance to stresses and induces mitochondrial ROS production through Complex I as signaling molecules to activate Ras and MAPK signaling, giving the survival advantages and adaptation to cancer cells. Finally, in silico and immunohistochemistry analysis showed that Lon is overexpressed specifically in various types of cancer tissue including oral cancer.
    Date: 2013-06
    Relation: Cell Death and Disease. 2013 Jun;4:Article number e681.
    Link to: http://dx.doi.org/10.1038/cddis.2013.204
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=2041-4889&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000321111700032
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84879678155
    Appears in Collections:[Alan Yueh-Luen Lee] Periodical Articles
    [Shih-Sheng Jiang] Periodical Articles

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