國家衛生研究院 NHRI:Item 3990099045/12356
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    Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/12356


    Title: Cancer-derived succinate promotes macrophage polarization and cancer metastasis via succinate receptor
    Authors: Wu, JY;Huang, TW;Hsieh, YT;Wang, YF;Yen, CC;Lee, GL;Yeh, CC;Peng, YJ;Kuo, YY;Wen, HT;Lin, HC;Hsiao, CW;Wu, KK;Kung, HJ;Hsu, YJ;Kuo, CC
    Contributors: Institute of Cellular and Systems Medicine;Institute of Molecular and Genomic Medicine
    Abstract: Macrophages form a major cell population in the tumor microenvironment. They can be activated and polarized into tumor-associated macrophages (TAM) by the tumor-derived soluble molecules to promote tumor progression and metastasis. Here, we used comparative metabolomics coupled with biochemical and animal studies to show that cancer cells release succinate into their microenvironment and activate succinate receptor (SUCNR1) signaling to polarize macrophages into TAM. Furthermore, the results from in vitro and in vivo studies revealed that succinate promotes not only cancer cell migration and invasion but also cancer metastasis. These effects are mediated by SUCNR1-triggered PI3K-hypoxia-inducible factor 1alpha (HIF-1alpha) axis. Compared with healthy subjects and tumor-free lung tissues, serum succinate levels and lung cancer SUCNR1 expression were elevated in lung cancer patients, suggesting an important clinical relevance. Collectively, our findings indicate that the secreted tumor-derived succinate belongs to a novel class of cancer progression factors, controlling TAM polarization and promoting tumorigenic signaling.
    Date: 2020-01
    Relation: Molecular Cell. 2020 Jan;77(2):213-227.e5.
    Link to: http://dx.doi.org/10.1016/j.molcel.2019.10.023
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1097-2765&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000507859300005
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85077737480
    Appears in Collections:[Cheng-Chin Kuo] Periodical Articles
    [Kenneth Kun-Yu Wu] Periodical Articles
    [Hsing-Jien Kung] Periodical Articles

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