MITOCHONDRIA: Succinate dehydrogenase subunit B-associated phaeochromocytoma and paraganglioma

Dona, Margo; Neijman, Kim; Timmers, Henri J L M

doi:10.1016/j.biocel.2021.105949

Cited by 5 publications

(4 citation statements)

References 27 publications

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“…SDH gene germline mutations lead to SDH-deficient renal cell carcinoma 139 . Moreover, SDH acts as a key regulator in neurodegenerative disorders 140 , neuroendocrine tumors 141 , Chronic obstructive pulmonary disease 142 . In addition, SDH is critical for metabolic and epigenetic regulation of T cell proliferation and inflammation, SDH deficiency induced a proinflammatory gene signature in T cells and promoted T helper 1 and T helper 17 lineage differentiation 143 .…”

Section: Mitochondrial Function In Cancer Cell Metabolismmentioning

confidence: 99%

An Overview: The Diversified Role of Mitochondria in Cancer Metabolism

Liu¹,

Sun²,

Guo³

et al. 2023

Int. J. Biol. Sci.

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Mitochondria are intracellular organelles involved in energy production, cell metabolism and cell signaling. They are essential not only in the process of ATP synthesis, lipid metabolism and nucleic acid metabolism, but also in tumor development and metastasis. Mutations in mtDNA are commonly found in cancer cells to promote the rewiring of bioenergetics and biosynthesis, various metabolites especially oncometabolites in mitochondria regulate tumor metabolism and progression. And mutation of enzymes in the TCA cycle leads to the unusual accumulation of certain metabolites and oncometabolites. Mitochondria have been demonstrated as the target for cancer treatment. Cancer cells rely on two main energy resources: oxidative phosphorylation (OXPHOS) and glycolysis. By manipulating OXPHOS genes or adjusting the metabolites production in mitochondria, tumor growth can be restrained. For example, enhanced complex I activity increases NAD + /NADH to prevent metastasis and progression of cancers. In this review, we discussed mitochondrial function in cancer cell metabolism and specially explored the unique role of mitochondria in cancer stem cells and the tumor microenvironment. Targeting the OXPHOS pathway and mitochondria-related metabolism emerging as a potential therapeutic strategy for various cancers.

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Section: Mitochondrial Function In Cancer Cell Metabolismmentioning

confidence: 99%

An Overview: The Diversified Role of Mitochondria in Cancer Metabolism

Liu¹,

Sun²,

Guo³

et al. 2023

Int. J. Biol. Sci.

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“…The SDHB gene encodes for SDHB protein assembled in the mitochondria to form succinate dehydrogenase (SDH), a key respiratory enzyme, that has an essential role in cell energy production. With absent or abnormal SDHB, the mitochondrial complex II fails to assemble and loses its enzymatic activity, causing the accumulation of succinate, inhibiting α-KG-dependent dioxygenases, and resulting in a pseudo hypoxic state, hypermethylation, and subsequent invasive behavior ( 23 ).…”

Section: Introductionmentioning

confidence: 99%

SDHB immunohistochemistry for prognosis of pheochromocytoma and paraganglioma: A retrospective and prospective analysis

Yang

Jiang

et al. 2023

Front. Endocrinol.

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IntroductionPheochromocytomas and paragangliomas (PCC/PGL) are rare neuroendocrine tumors and can secrete catecholamine. Previous studies have found that SDHB immunohistochemistry (IHC) can predict SDHB germline gene mutation, and SDHB mutation is closely associated with tumor progression and metastasis. This study aimed to clarify the potential effect of SDHB IHC as a predictive marker for tumor progression in PCC/PGL patients.MethodsWe included PCC/PGL patients diagnosed in Ruijin Hospital, Shanghai Jiao Tong University School of Medicine from 2002 to 2014 for retrospective analysis and discovered that SDHB (-) staining patients had poorer prognoses. Then we examined SDHB protein expression by IHC on all tumors in the prospective series, which was composed of patients from 2015 to 2020 in our center.ResultsIn the retrospective series, the median follow-up was 167 months, and during follow-up, 14.4% (38/264) patients developed metastasis or recurrence, and 8.0% (22/274) patients died. Retrospective analysis revealed that 66.7% (6/9) of participants in the SDHB (-) group and 15.7% (40/255) of those in the SDHB (+) group developed progressive tumors (OR: 10.75, 95% CI: 2.72-52.60, P=0.001), and SDHB (-) was independently associated with poor outcomes after adjusting by other clinicopathological parameters (OR: 11.68, 95% CI: 2.58-64.45, P=0.002). SDHB (-) patients had shorter disease-free survival (DFS) and overall survival (OS) (P<0.001) and SDHB (-) was significantly associated with shorter median DFS (HR: 6.89, 95% CI: 2.41-19.70, P<0.001) in multivariate cox proportional hazard analysis. In the prospective series, the median follow-up was 28 months, 4.7% (10/213) patients developed metastasis or recurrence, and 0.5% (1/217) patient died. For the prospective analysis, 18.8% (3/16) of participants in the SDHB (-) group had progressive tumors compared with 3.6% (7/197) in the SDHB (+) group (RR: 5.28, 95% CI: 1.51-18.47, P=0.009), statistical significance remained (RR: 3.35, 95% CI: 1.20-9.38, P=0.021) after adjusting for other clinicopathological factors.ConclusionsOur findings demonstrated patients with SDHB (-) tumors had a higher possibility of poor outcomes, and SDHB IHC can be regarded as an independent biomarker of prognosis in PCC/PGL.

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“…For example, oncometabolites lead to extensive hypermethylation of histone 3 lysine 9 (H3K9me3) by inhibiting histone lysine demethylase (KDM), which hinders the recruitment of DNA repair factors, leading to genomic instability that promotes tumor growth [ 112 ]. Thus, fumarate, succinate, D-2HG, and L-2HG have been characterized as bona fide tumor metabolites and have become pathognomonic hallmarks of a growing number of cancers ( Figure 3 ), including neuroendocrine tumors, gliomas, leukemia, renal cell carcinomas, and head and neck squamous cell carcinomas [ 113 , 114 , 115 , 116 ]. In recent years, there has been great interest in the possible role of oncometabolites in cancer cell resistance to radiation, and numerous clinical trials have been conducted.…”

Section: Oncometabolites and Radioresistancementioning

confidence: 99%

Targeting Mitochondrial Metabolism to Reverse Radioresistance: An Alternative to Glucose Metabolism

Bian

Zheng

et al. 2022

Antioxidants

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Radiotherapy failure and poor tumor prognosis are primarily attributed to radioresistance. Improving the curative effect of radiotherapy and delaying cancer progression have become difficult problems for clinicians. Glucose metabolism has long been regarded as the main metabolic process by which tumor cells meet their bioenergetic and anabolic needs, with the complex interactions between the mitochondria and tumors being ignored. This misconception was not dispelled until the early 2000s; however, the cellular molecules and signaling pathways involved in radioresistance remain incompletely defined. In addition to being a key metabolic site that regulates tumorigenesis, mitochondria can influence the radiation effects of malignancies by controlling redox reactions, participating in oxidative phosphorylation, producing oncometabolites, and triggering apoptosis. Therefore, the mitochondria are promising targets for the development of novel anticancer drugs. In this review, we summarize the internal relationship and related mechanisms between mitochondrial metabolism and cancer radioresistance, thus exploring the possibility of targeting mitochondrial signaling pathways to reverse radiation insensitivity. We suggest that attention should be paid to the potential value of mitochondria in prolonging the survival of cancer patients.

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MITOCHONDRIA: Succinate dehydrogenase subunit B-associated phaeochromocytoma and paraganglioma

Cited by 5 publications

References 27 publications

An Overview: The Diversified Role of Mitochondria in Cancer Metabolism

An Overview: The Diversified Role of Mitochondria in Cancer Metabolism

SDHB immunohistochemistry for prognosis of pheochromocytoma and paraganglioma: A retrospective and prospective analysis

Targeting Mitochondrial Metabolism to Reverse Radioresistance: An Alternative to Glucose Metabolism

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