Succinate dehydrogenase B‐deficient renal cell carcinoma: A case report with novel germline mutation

Iwashita, Hiromichi; Okihara, Koji; Matsumura, Mai; Yamanaka, Shōji; Sawazumi, Tomoe; Enaka, Makiko; Udaka, Naoko; Miyake, Akio; Hibiya, Takashi; Miyake, Noriko; Matsumoto, Naomichi; Makiyama, Kazuhide; Yao, Masahiro; Nagashima, Yoji; Ohashi, Kenichi

doi:10.1111/pin.12587

Cited by 7 publications

(7 citation statements)

References 10 publications

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“…Aberrant TCA cycle function is implicated in a wide variety of pathological processes such as obesity. Moreover, several TCA cycle enzymes are deregulated in cancer (Figure 3) [63][64][65][66][67][68][69][70][71][72][73][74][75][76][77][78][79][80][81][82]. tumour cells, which require a continuous supply of small metabolites for the synthesis of proteins, nucleic acids, and lipids.…”

Section: Introductionmentioning

confidence: 99%

“…Aberrant TCA cycle function is implicated in a wide variety of pathological processes such as obesity. Moreover, several TCA cycle enzymes are deregulated in cancer (Figure 3) [63][64][65][66][67][68][69][70][71][72][73][74][75][76][77][78][79][80][81][82]. The electron transport chain (ETC) controls combustion, which generates energy to be used to drive the oxidation of NADH, which produces three ATP molecules and FADH2 (which produces two ATP molecules) at the expense of reducing oxygen.…”

Section: Introductionmentioning

confidence: 99%

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Energy Metabolism in Cancer: The Roles of STAT3 and STAT5 in the Regulation of Metabolism-Related Genes

Valle‐Mendiola¹,

Soto‐Cruz²

2020

Cancers

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A central characteristic of many types of cancer is altered energy metabolism processes such as enhanced glucose uptake and glycolysis and decreased oxidative metabolism. The regulation of energy metabolism is an elaborate process involving regulatory proteins such as HIF (pro-metastatic protein), which reduces oxidative metabolism, and some other proteins such as tumour suppressors that promote oxidative phosphorylation. In recent years, it has been demonstrated that signal transducer and activator of transcription (STAT) proteins play a pivotal role in metabolism regulation. STAT3 and STAT5 are essential regulators of cytokine- or growth factor-induced cell survival and proliferation, as well as the crosstalk between STAT signalling and oxidative metabolism. Several reports suggest that the constitutive activation of STAT proteins promotes glycolysis through the transcriptional activation of hypoxia-inducible factors and therefore, the alteration of mitochondrial activity. It seems that STAT proteins function as an integrative centre for different growth and survival signals for energy and respiratory metabolism. This review summarises the functions of STAT3 and STAT5 in the regulation of some metabolism-related genes and the importance of oxygen in the tumour microenvironment to regulate cell metabolism, particularly in the metabolic pathways that are involved in energy production in cancer cells.

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Section: Introductionmentioning

confidence: 99%

“…Aberrant TCA cycle function is implicated in a wide variety of pathological processes such as obesity. Moreover, several TCA cycle enzymes are deregulated in cancer (Figure 3) [63][64][65][66][67][68][69][70][71][72][73][74][75][76][77][78][79][80][81][82]. The electron transport chain (ETC) controls combustion, which generates energy to be used to drive the oxidation of NADH, which produces three ATP molecules and FADH2 (which produces two ATP molecules) at the expense of reducing oxygen.…”

Section: Introductionmentioning

confidence: 99%

Energy Metabolism in Cancer: The Roles of STAT3 and STAT5 in the Regulation of Metabolism-Related Genes

Valle‐Mendiola¹,

Soto‐Cruz²

2020

Cancers

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“…The mutations in SDHA, SDHC and SDHD genes are less frequent. Up to date only 59 SDH-deficient RCC cases have been described [2][3][4][5][6].…”

Section: Implications For Practicementioning

confidence: 99%

“…Mutations in the SDHA , SDHC , and SDHD genes are less frequent. Until now only 59 SDH‐deficient RCC cases have been described [2–6]. Patients’ ages at diagnosis ranged from 14 to 76 years.…”

Section: Introductionmentioning

confidence: 99%

Succinate Dehydrogenase-Deficient Renal Cancer Featuring Fructose-1,6-Biphosphatase Loss, Pyruvate Kinase M2 Overexpression, and SWI/SNF Chromatin Remodeling Complex Aberrations: A Rare Case Report

et al. 2021

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SDH (succinate dehydrogenase)-deficient renal cancer is a rare renal cancer (RCC) subtype recently accepted by WHO as an unique RCC subtype with only 59 cases described worldwide. Here we report a case of 17-year old man. The detailed evaluation indicated occurrence of the SDHBdeficient RCC. The genetic testing revealed no germline mutation in SDH genes. Immunohistochemistry showed SDHB deficiency, overexpression of PKM2 and dramatic downregulation of FBP1 metabolic enzymes, unaltered levels of pAMPK and mTOR. Furthermore, the strong upregulation of INI1, BRG1 and overexpression of BAF180 subunits of SWI/SNF ATP-dependent chromatin remodeling complex were found. The identified tumor pathologically did not resemble ccRCC (clear cell renal cell carcinoma) but some metabolic alterations are common for both cancer types. Thus, we postulate that the phenotypical differences between ccRCC and SDHB-deficient RCC may be related to distinct molecular and metabolic alterations.

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“…Succinate dehydrogenase (SDH), a heterotetrametric complex, which includes SDHA, SDHB, SDHC and SDHD is an important citric acid cycle enzyme in mitochondria [9–11]. SDH is engaged in the oxidation of succinate to fumarate and in the electron transport [12, 13].…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-96-3p promotes metastasis of papillary thyroid cancer through targeting SDHB

Zhao

Zhou

2019

Cancer Cell Int

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BackgroundMicroRNA (MiRNA) is a small non-coding RNA which is implicated in a cohort of biological function in cancer, including proliferation, metastasis, apoptosis and invasion. MiR-96 has been reported to be involved in many cancers, including papillary thyroid cancer. However, the role of miR-96-3p in papillary thyroid cancer metastasis is still unclear.MethodsqRT-PCR is used to detect the level of miR-96-3p and mRNA of SDHB in PTC tissues and cell lines. Western blot assays are used to verify the protein expression of SDHB. The transwell assays are performed to identify the migration ability of PTC cell lines. Moreover, dual-luciferase 3′-UTR reporter assays are chosen to illuminate the direct target of miR-96-3p.ResultsThe relative miR-96-3p upregulate in PTC tissues and three PTC cell lines (B-CPAP, K-1 and TPC-1 cells) while the relative SDHB is opposite. Our results revealed that the miR-96-3p promotes metastasis and invasion in PTC cell lines (K-1 and TPC-1 cells) by direct targeting SDHB and influence the downstream protein AKT.ConclusionsTaken together, the miR-96-3p is involved in PTC metastasis and invasion by direct targeting SDHB and the downstream molecule AKT and mTOR.

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Succinate dehydrogenase B‐deficient renal cell carcinoma: A case report with novel germline mutation

Cited by 7 publications

References 10 publications

Energy Metabolism in Cancer: The Roles of STAT3 and STAT5 in the Regulation of Metabolism-Related Genes

Energy Metabolism in Cancer: The Roles of STAT3 and STAT5 in the Regulation of Metabolism-Related Genes

Succinate Dehydrogenase-Deficient Renal Cancer Featuring Fructose-1,6-Biphosphatase Loss, Pyruvate Kinase M2 Overexpression, and SWI/SNF Chromatin Remodeling Complex Aberrations: A Rare Case Report

MicroRNA-96-3p promotes metastasis of papillary thyroid cancer through targeting SDHB

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