Chia Nan University of Pharmacy & Science Institutional Repository:Item 310902800/32253
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    Title: Decreased succinate dehydrogenase B in human hepatocellular carcinoma accelerates tumor malignancy by inducing the Warburg effect
    Authors: 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
    Contributors: 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
    Keywords: Sdhd Gene-Mutations
    Mammalian-Cells
    Germline Sdhb
    Cancer
    Expression
    Paraganglioma
    Hexokinase
    Subunit
    Pheochromocytoma
    Activation
    Date: 2018-02-15
    Issue Date: 2019-11-15 15:46:57 (UTC+8)
    Publisher: NATURE PUBLISHING GROUP
    Abstract: 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.
    ???metadata.dc.relation.uri???: http://dx.doi.org/10.1038/s41598-018-21361-6
    Relation: Scientific Reports, v.8, 3081
    Appears in Collections:[Dept. of Occupational Safety] Periodical Articles

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