國家衛生研究院 NHRI:Item 3990099045/12488
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    Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/12488


    Title: Mitochondrial oxidative stress by Lon-PYCR1 maintains an immunosuppressive tumor microenvironment that promotes cancer progression and metastasis
    Authors: Kuo, CL;Chou, HY;Chiu, YC;Cheng, AN;Fan, CC;Chang, YN;Chen, CH;Jiang, SS;Chen, NJ;Yueh-Luen Lee, A
    Contributors: National Institute of Cancer Research;Institute of Population Health Sciences
    Abstract: Mitochondrial Lon is a chaperone protein whose upregulation increases the production of mitochondrial reactive oxygen species (ROS). However, there is a lack of information in detail on how mitochondrial Lon regulates cancer metastasis through ROS production in the tumor microenvironment (TME). Our results show that elevated Lon promotes epithelial-mesenchymal transition (EMT) via ROS-dependent p38 and NF-kappaB-signaling. We further identified pyrroline-5-carboxylate reductase 1 (PYCR1) as a client of chaperone Lon, which induces mitochondrial ROS and EMT by Lon. Mitochondrial Lon induces ROS-dependent production of inflammatory cytokines, such as TGF-beta, IL-6, IL-13, and VEGF-A, which consequently activates EMT, angiogenesis, and M2 macrophage polarization. In addition, Lon expression is induced upon the activation and M2 polarization of macrophages, which further promotes M2 macrophages to enhance the immunosuppressive microenvironment and metastatic behaviors in the TME. This raises the possibility that manipulation of the mitochondrial redox balance in the TME may serve as a therapeutic strategy to improve T cell function in cancer immunotherapy.
    Date: 2020-01-24
    Relation: Cancer Letters. 2020 Jan 24;474:138-150.
    Link to: http://dx.doi.org/10.1016/j.canlet.2020.01.019
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0304-3835&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000518673300013
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85078407089
    Appears in Collections:[Alan Yueh-Luen Lee] Periodical Articles
    [Shih-Sheng Jiang] Periodical Articles
    [Others] Periodical Articles

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