Analysis of succinate dehydrogenase subunit B gene alterations in gastric cancers

Cao, Zhiyun; Song, Jae Yen; Kang, Young Whi; Yoon, Jung Hwan; Nam, Suk Woo; Lee, Jung Young; Park, Won Sang

doi:10.1111/j.1440-1827.2010.02558.x

Cited by 6 publications

(4 citation statements)

References 33 publications

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“…Levels of SDHB are significantly decreased in human colon cancer tissues, and this is associated with tumor cell dedifferentiation 25 . SDHB showed reduced or loss of expression in 24.5% of gastric cancers but was not associated with clinical parameters, such as tumor invasion and differentiation 27 . A recent study also revealed decreased SDHB expression (48%) in HCC 28 .…”

Section: Discussionmentioning

confidence: 87%

“…Germline mutations of SDHB were also associated with renal cell carcinoma, but not always with different morphologies 24 . SDHB expression has also been investigated in other general solid tumors, such as colon, gastric and breast cancers 25 – 27 . Levels of SDHB are significantly decreased in human colon cancer tissues, and this is associated with tumor cell dedifferentiation 25 .…”

Section: Discussionmentioning

confidence: 99%

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

Tseng

et al. 2018

Sci Rep

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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.

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Section: Discussionmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 99%

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

Tseng

et al. 2018

Sci Rep

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“…It is also possible that aberrant H3K27me3 regulation in immortal and tumorigenic cells is a consequence of altered energy metabolism in those cells. Many cancers have increased glycolysis and reduced tricarboxylic acid (TCA) cycle activity (30)(31)(32), which can lead to accumulation of succinate that in turn inhibits the H3K27 demethylase JMJD3 (33). Additionally, impaired TCA cycle use might result in reduced conversion of isocitrate to α-ketoglutarate, potentially limiting activities of H3K27 demethylases requiring this cofactor (34).…”

Section: Discussionmentioning

confidence: 99%

Single-molecule analysis of combinatorial epigenomic states in normal and tumor cells

Murphy

Cipriany²,

Wallin³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Proper placement of epigenetic marks on DNA and histones is fundamental to normal development, and perturbations contribute to a variety of disease states. Combinations of marks act together to control gene expression; therefore, detecting their colocalization is important, but because of technical challenges, such measurements are rarely reported. Instead, measurements of epigenetic marks are typically performed one at a time in a population of cells, and their colocalization is inferred by association. Here, we describe a single-molecule analytical approach that can perform direct detection of multiple epigenetic marks simultaneously and use it to identify mechanisms coordinating placement of three gene silencing marks, trimethylated histone H3 lysine 9, lysine 27 (H3K9me3, H3K27me3), and cytosine methylation (mC), in the normal and cancer genome. We show that H3K9me3 and mC are present together on individual chromatin fragments in mouse embryonic stem cells and that half of the H3K9me3 marks require mC for their placement. In contrast, mC and H3K27me3 coincidence is rare, and in fact, mC antagonizes H3K27me3 in both embryonic stem cells and primary mouse fibroblasts, indicating this antagonism is shared among primary cells. However, upon immortalization or tumorigenic transformation of mouse fibroblasts, mC is required for complete H3K27me3 placement. Importantly, in human promyelocytic cells, H3K27me3 is also dependent on mC. Because aberrant placement of gene silencing marks at tumor suppressor genes contributes to tumor progression, the improper dependency of H3K27me3 by mC in immortalized cells is likely to be fundamental to cancer. Our platform can enable other studies involving coordination of epigenetic marks and leverage efforts to discover disease biomarkers and epigenome-modifying drugs.

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“…Defective OXPHOS may be driven by mutations in genes encoding its components. Mutations in nuclear genes encoding subunits of succinate dehydrogenase or proteins involved in assembling OXPHOS complex II are associated with hereditary cancers (Ricketts et al, 2012;Cao et al, 2010). Also alterations in the mitochondria-encoded OXPHOS genes are associated with invasive properties in human cancer cell lines.…”

Section: Changes In Oxidative Phosphorylation In Pre-cancerous Lesionmentioning

confidence: 99%

Role of mitochondria in carcinogenesis.

Tokarz

Błasiak

2014

Acta Biochim Pol

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Mitochondria play the central role in supplying cells with ATP and are also the major source of reactive oxygen species (ROS) - molecules of both regulatory and destructive nature. Dysfunction of mitochondrial metabolism and/or morphology have been frequently reported in human cancers. This dysfunction can be associated with mitochondrial DNA (mtDNA) damage, which may be changed into mutations in mtDNA coding sequences, or the displacement-loop region, changes in the mtDNA copy number or mtDNA microsatellite instability. All these features are frequently associated with human cancers. Mutations in mtDNA can disturb the functioning of the ROS-producing organelle and further affect the entire cell which may contribute to genomic instability typical for cancer cells. Although the association between some mtDNA mutations and cancer is well established, the causative relationship between these two features is largely unknown. A hint suggesting the driving role of mtDNA mutations in carcinogenesis comes from the observation of tumor promotion after mtDNA depletion. Mitochondria with damaged DNA may alter signaling of the mitochondrial apoptosis pathway promoting cancer cell survival and conferring resistance to anticancer drugs. This resistance may be underlined by mtDNA copy number depletion. Therefore, mitochondria are considered a promising target in anticancer therapy and several mitochondria-targeting drugs are in preclinical and clinical trials. Some other aspects of mitochondrial structure and functions, including morphology and redox potential, can also be associated with cancer transformation and constitute new anticancer targets. Recently, several studies have disclosed new mechanisms underlying the association between mitochondria and cancer, including the protection of mtDNA by telomerase, suggesting new approaches in mitochondria-oriented anti-cancer therapy.

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Analysis of succinate dehydrogenase subunit B gene alterations in gastric cancers

Cited by 6 publications

References 33 publications

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

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

Single-molecule analysis of combinatorial epigenomic states in normal and tumor cells

Role of mitochondria in carcinogenesis.

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