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

Po Lin Tseng, Wei Hsuan Wu, Tsung Hui Hu, Chih Wei Chen, Hung Chi Cheng, Chien Feng Li, Wen Hui Tsai, Hui Ju Tsai, Meng Che Hsieh, Jiin Haur Chuang, Wen Tsan Chang

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Article number3081
JournalScientific reports
Volume8
Issue number1
DOIs
Publication statusPublished - 2018 Dec 1

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Succinate Dehydrogenase
Hepatocellular Carcinoma
Neoplasms
Glycolysis
Energy Metabolism
Cell Movement
Respiration
Cell Dedifferentiation
Cell Proliferation
Tumor Burden
Heterografts
Tail
Veins
Survival Rate
Neoplasm Metastasis
Mutation
Injections
Survival
Enzymes
Growth

All Science Journal Classification (ASJC) codes

  • General

Cite this

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. / Decreased succinate dehydrogenase B in human hepatocellular carcinoma accelerates tumor malignancy by inducing the Warburg effect. In: Scientific reports. 2018 ; Vol. 8, No. 1.
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Decreased succinate dehydrogenase B in human hepatocellular carcinoma accelerates tumor malignancy by inducing the Warburg effect. / 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.

In: Scientific reports, Vol. 8, No. 1, 3081, 01.12.2018.

Research output: Contribution to journalArticle

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AU - Chen, Chih Wei

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AU - Li, Chien Feng

AU - Tsai, Wen Hui

AU - Tsai, Hui Ju

AU - Hsieh, Meng Che

AU - Chuang, Jiin Haur

AU - Chang, Wen Tsan

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