Decreased succinate dehydrogenase B in human hepatocellular carcinoma accelerates tumor malignancy by inducing the Warburg effect

doi:10.1038/s41598-018-21361-6

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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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