Pheochromocytoma: Gasping for Air

Jochmanová, Ivana; Zhuang, Zhengping; Pacák, Karel

doi:10.1007/s12672-015-0231-4

Cited by 30 publications

(28 citation statements)

References 210 publications

(155 reference statements)

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“…For instance, mutations in genes encoding the succinate dehydrogenase (SDH) complex subunits ( SDHx: SDHA, SDHB, SDHC, SDHD ), fumarate hydratase ( FH ), isocitrate dehydrogenase ( IDH ), and malate dehydrogenase ( MDH ) are known to cause accumulation of Krebs cycle metabolites/substrates, such as succinate, pyruvate, fumarate, citrate, or glutamine, which can promote tumorigenesis via generation of pseudohypoxic state (i.e. hypoxia-inducible factors (HIFs) signaling activation), epigenetic alterations, and dysregulation of other metabolic processes; reviewed in (24). …”

Section: Mitochondria Krebs Cycle and Cancer Cell Metabolismmentioning

confidence: 99%

“…These effects are, in part, mediated through oxygen independent HIF-α stabilization and activation of HIF signaling. Decreased oxygen availability (hypoxia) or conditions leading to stabilization of HIF-α, even in the presence of sufficient amount of oxygen (pseudohypoxia), trigger the switch of metabolism from OXPHOS to glycolysis (18, 24, 43, 44). …”

Section: Mitochondria Krebs Cycle and Cancer Cell Metabolismmentioning

confidence: 99%

“…For instance, citrate, under physiological conditions, slows down/inhibits the Krebs cycle and glycolysis, and stimulates gluconeogenesis and lipid synthesis. Moreover, ATP-citrate lyase, the cytosolic enzyme amenable for citrate cleavage to oxaloacetate and acetyl-CoA, is involved in metabolic regulation of the PI3K/Akt/mTOR pathway (6, 24, 74). Loss of the citrate synthase enzyme, and thus, decrease of citrate levels, was also linked to the induction of epithelial-to-mesenchymal transition, which confers to cancer cell invasion and metastasis (75).…”

Section: Metabolic Alterations In Pheos/pglsmentioning

confidence: 99%

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Pheochromocytoma: The First Metabolic Endocrine Cancer

Jochmanová

Pacák

2016

Clinical Cancer Research

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Dysregulated metabolism is one of the key characteristics of cancer cells. The most prominent alterations are present during regulation of cell respiration, which leads to a switch from oxidative phosphorylation to aerobic glycolysis. This metabolic shift results in activation of numerous signaling and metabolic pathways supporting cell proliferation and survival. Recent progress in genetics and metabolomics allowed us to take a closer look at the metabolic changes present in pheochromocytomas and paragangliomas (PHEOs/PGLs). These neuroendocrine tumors often exhibit dysregulation of mitochondrial metabolism, which is driven by mutations in genes encoding Krebs cycle enzymes or by activation of hypoxia signaling. Present metabolic changes are involved in processes associated with tumorigenesis, invasiveness, metastasis, and resistance to various cancer therapies. In this review, we discuss the metabolic nature of PHEOs/PGLs and how unveiling the metabolic disturbances present in tumors could lead to identification of new biomarkers and personalized cancer therapies.

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Section: Mitochondria Krebs Cycle and Cancer Cell Metabolismmentioning

confidence: 99%

Section: Mitochondria Krebs Cycle and Cancer Cell Metabolismmentioning

confidence: 99%

Section: Metabolic Alterations In Pheos/pglsmentioning

confidence: 99%

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Pheochromocytoma: The First Metabolic Endocrine Cancer

Jochmanová

Pacák

2016

Clinical Cancer Research

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“…It has been shown that hypoxia-induced calcium levels and responses are mediated preferentially by IP 3 receptors [17,18]. Activation of the hypoxia-inducible transcription factor (HIF) signaling pathway is also involved in the tumorigenesis, invasiveness, and metastatic spread [19,20]. Activated hypoxic pathways are associated with resistance to various cancer therapies and significantly worsen the patient's prognosis.…”

Section: Introductionmentioning

confidence: 99%

Hypoxic conditions increases H2S-induced ER stress in A2870 cells

2016

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Hypoxia - a state of lower oxygen demand-is responsible for a higher aggressiveness of tumors and therefore a worse prognosis. During hypoxia, several metabolic pathways are re-organized, e.g., energetic metabolism, modulation of pH, and calcium transport. Calcium is an important second messenger that regulates variety of processes in the cell. Thus, aim of this work was to compare H2S modulation of the intracellular calcium transport systems in hypoxia and in cells grown in standard culture conditions. For all experiments, we used ovarian cancer cell line (A2780). H2S is a novel gasotransmitter, known to be involved in a modulation of several calcium transport systems, thus resulting in altered calcium signaling. Two models of hypoxia were used in our study-chemical (induced by dimethyloxallyl glycine) and 2 % O2 hypoxia, both combined with a treatment using a slow H2S donor GYY4137. In hypoxia, we observed rapid changes in cytosolic and reticular calcium levels compared to cells grown in standard culture conditions, and these changes were even more exagerrated when combined with the GYY4137. Changes in a calcium homeostasis result from IP3 receptor´s up-regulation and down-regulation of the SERCA 2, which leads to a development of the endoplasmic reticulum stress. Based on our results, we propose a higher vulnerability of calcium transport systems to H2S regulation under hypoxia.

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“…Mutations or loss of heterozygosity of the genes SDHA, SDHB, SDHC, and SDHD have been described in paragangliomas, pheochromocytomas [19,20,21,22], renal cell carcinoma [19,23,24], gastrointestinal carcinoma [19], familial pheochromocytoma and paraganglioma [14,24,25,26,27], Cowden's syndrome [22,23], medullar [1,19] and papillary thyroid carcinoma [14,19,24], and more recently pituitary adenomas [28,29,30]. …”

Section: Introductionmentioning

confidence: 99%

Familiar Papillary Thyroid Carcinoma in a Large Brazilian Family Is Not Associated with Succinate Dehydrogenase Defects

et al. 2016

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Background: Thyroid cancer is the most common endocrine gland malignancy. Advances in understanding the genetic basis for thyroid cancer revealed the potential involvement of several genes in the formation of thyroid tumors. Mutations in the gene coding for succinate dehydrogenase subtype B (SDHB) have been implicated in papillary thyroid cancer (PTC). Succinate dehydrogenase (SDH) is a heterotetrameric protein composed of four subunits, SDHA,SDHB,SDHC, and SDHD, and participates in both the electron transport chain and the tricarboxylic acid cycle. The aim of the study was to evaluate the association between variants in the SDHA,SDHB,SDHC, and SDHD genes and familiar PTC in a large Brazilian family. Method: Four patients with PTC, 1 patient with PTC and gastrointestinal stromal tumor (GIST), 1 patient with GIST, and their relatives - several of them with different thyroid problems - from a large Brazilian family were screened for genetic variations of SDHx genes with the use of polymerase chain reaction-single-stranded conformational polymorphism and direct sequencing. Results: Only one rare variation in SDHA was found in some of the family members, but not segregating with the disease. No other genetic variants of these genes were detected in the family members that presented with PTC and/or GIST. Conclusion: Familiar PTC and a GIST were not associated with SDHx mutations; additional genetic defects, yet unknown, may be responsible for the development of tumor.

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Pheochromocytoma: Gasping for Air

Cited by 30 publications

References 210 publications

Pheochromocytoma: The First Metabolic Endocrine Cancer

Pheochromocytoma: The First Metabolic Endocrine Cancer

Hypoxic conditions increases H2S-induced ER stress in A2870 cells

Familiar Papillary Thyroid Carcinoma in a Large Brazilian Family Is Not Associated with Succinate Dehydrogenase Defects

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