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| 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
Mammalian-Cells
Germline Sdhb
Cancer
Expression
Paraganglioma
Hexokinase
Subunit
Pheochromocytoma
Activation |
| 日期: | 2018-02-15 |
| 上傳時間: | 2019-11-15 15:46:57 (UTC+8) |
| 出版者: | NATURE PUBLISHING GROUP |
| 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 |
| 顯示於類別: | [職業安全衛生系(含防災所)] 期刊論文
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