國家衛生研究院 NHRI:Item 3990099045/11107
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    Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/11107


    Title: Transketolase regulates the metabolic switch to control breast cancer cell metastasis via the alpha-ketoglutarate signaling pathway
    Other Titles: Transketolase regulates the metabolic switch to control breast cancer cell metastasis via the α-ketoglutarate signaling pathway
    Authors: Tseng, CW;Kuo, WH;Chan, SH;Chan, HL;Chang, KJ;Wang, LH
    Contributors: Institute of Molecular and Genomic Medicine
    Abstract: Although metabolic reprogramming is recognized as a hallmark of tumorigenesis and progression, little is known about metabolic enzymes and oncometabolites that regulate breast cancer metastasis, and very few metabolic molecules have been identified as potential therapeutic targets. In this study, the transketolase (TKT) expression correlated with tumor size in the 4T1/BALB/c syngeneic model. In addition, TKT expression was higher in lymph node metastases compared with primary tumor or normal tissues of patients, and high TKT levels were associated with poor survival. Depletion of TKT or addition of alpha-ketoglutarate (alpha-KG) enhanced the levels of tumor suppressors succinate dehydrogenase (SDH) and fumarate hydratase (FH), decreasing oncometabolites succinate and fumarate and further stabilizing HIF prolyl hydroxylase 2 (PHD2) and decreasing HIF-1alpha, ultimately suppressing breast cancer metastasis. Reduced TKT or addition of alpha-KG mediated a dynamic switch of glucose metabolism from glycolysis to oxidative phosphorylation. Various combinations of the TKT inhibitor oxythiamine, docetaxel, and doxorubicin enhanced cell death in triple-negative breast cancer (TNBC) cells. Furthermore, oxythiamine treatment led to increased levels of alpha-KG in TNBC cells. Together, our study has identified a novel TKT-mediated alpha-KG signaling pathway that regulates breast cancer oncogenesis and can be exploited as a modality for improving therapy.
    Date: 2018-06
    Relation: Cancer Research. 2018 Jun;78(11):2799-2812.
    Link to: http://dx.doi.org/10.1158/0008-5472.Can-17-2906
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0008-5472&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000433930700003
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85048040586
    Appears in Collections:[Lu-Hai Wang] Periodical Articles

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