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    Please use this identifier to cite or link to this item: http://ir.cnu.edu.tw/handle/310902800/32253

    標題: Decreased succinate dehydrogenase B in human hepatocellular carcinoma accelerates tumor malignancy by inducing the Warburg effect
    作者: Tseng, Po-Lin
    Wu, Wei-Hsuan
    Hu, Tsung-Hui
    Chen, Chih-Wei
    Cheng, Hung-Chi
    Li, Chien-Feng
    Tsai, Wen-Hui
    Tsai, Hui-Ju
    Hsieh, Meng-Che
    Chuang, Jiin-Haur
    Chang, Wen-Tsan
    貢獻者: Chang Gung Univ, Coll Med, Grad Inst Clin Med Sci
    Natl Cheng Kung Univ, Coll Med, Dept Biochem & Mol Biol
    Chang Gung Mem Hosp, Kaohsiung Med Ctr, Dept Internal Med, Div Hepatogastroenterol
    Natl Cheng Kung Univ, Coll Med, Inst Clin Med
    Chi Mei Fdn, Med Ctr, Dept Pathol
    Chi Mei Fdn, Med Ctr, Dept Pediat
    Kaohsiung Chang Gung Mem Hosp, Kaohsiung Med Ctr, Dept Pediat Surg
    Chi Mei Fdn, Med Ctr, Dept Surg
    Chia Nan Univ Pharm & Sci, Coll Sustainable Environm, Inst Ind Safety & Disaster Prevent, Dept Occupat Safety & Hlth
    關鍵字: Sdhd Gene-Mutations
    Germline Sdhb
    日期: 2018-02-15
    上傳時間: 2019-11-15 15:46:57 (UTC+8)
    摘要: Changes in TCA cycle enzymes or respiratory activity are possible mechanisms of aerobic glycolysis that contributes to tumor progression. To clarify whether the decrease of succinate dehydrogenase B (SDHB) alters energy metabolism, induces the Warburg effect and results in tumor malignancy, SDHB expression was examined and modulated in hepatocellular carcinoma (HCC) tissues and cells, respectively. SDHB level was often decreased in malignant HCC cells and tissues. Furthermore, the reduced SDHB expression was associated with advanced tumor stage and poor survival rate. Moreover, silencing of SDHB altered energy metabolism switched from aerobic respiration to glycolysis, resulted in the Warburg effect, and enhanced cell proliferation and motility. In contrast, the SDHB overexpression deregulated bioenergetic metabolism and decreased cell growth and migration. In mouse xenograft models, subcutaneous implantation and tail vein injection with SDHB knockdown cells resulted in a larger tumor volume and accelerated cancer metastasis, respectively. A mutation or decrease in SDHB induced the switch from aerobic respiration to glycolysis. This metabolic alteration was associated with tumor cell dedifferentiation, proliferation, motility and overall patient survival in HCC.
    link: http://dx.doi.org/10.1038/s41598-018-21361-6
    關聯: Scientific Reports, v.8, 3081
    Appears in Collections:[職業安全衛生系(含防災所)] 期刊論文

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