Mitochondrial Dysfunction Pathway Networks and Mitochondrial Dynamics in the Pathogenesis of Pituitary Adenomas

Li, Na; Zhan, Xianquan

doi:10.3389/fendo.2019.00690

Cited by 29 publications

(27 citation statements)

References 142 publications

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“…Thus, with such a significant cellular role, dysfunction of the mitochondria has been shown to be related to various diseases, including cancer 3 . Mitochondrial dysfunction alters cellular energy metabolism, which contributes to carcinogenesis and tumor development 4 , 27 , 28 .…”

Section: Role Of Mitochondrial Dysfunction In Cancer Developmentmentioning

confidence: 99%

The crosstalk between HIFs and mitochondrial dysfunctions in cancer development

et al. 2021

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Mitochondria are essential cellular organelles that are involved in regulating cellular energy, metabolism, survival, and proliferation. To some extent, cancer is a genetic and metabolic disease that is closely associated with mitochondrial dysfunction. Hypoxia-inducible factors (HIFs), which are major molecules that respond to hypoxia, play important roles in cancer development by participating in multiple processes, such as metabolism, proliferation, and angiogenesis. The Warburg phenomenon reflects a pseudo-hypoxic state that activates HIF-1α. In addition, a product of the Warburg effect, lactate, also induces HIF-1α. However, Warburg proposed that aerobic glycolysis occurs due to a defect in mitochondria. Moreover, both HIFs and mitochondrial dysfunction can lead to complex reprogramming of energy metabolism, including reduced mitochondrial oxidative metabolism, increased glucose uptake, and enhanced anaerobic glycolysis. Thus, there may be a connection between HIFs and mitochondrial dysfunction. In this review, we systematically discuss the crosstalk between HIFs and mitochondrial dysfunctions in cancer development. Above all, the stability and activity of HIFs are closely influenced by mitochondrial dysfunction related to tricarboxylic acid cycle, electron transport chain components, mitochondrial respiration, and mitochondrial-related proteins. Furthermore, activation of HIFs can lead to mitochondrial dysfunction by affecting multiple mitochondrial functions, including mitochondrial oxidative capacity, biogenesis, apoptosis, fission, and autophagy. In general, the regulation of tumorigenesis and development by HIFs and mitochondrial dysfunction are part of an extensive and cooperative network.

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Section: Role Of Mitochondrial Dysfunction In Cancer Developmentmentioning

confidence: 99%

The crosstalk between HIFs and mitochondrial dysfunctions in cancer development

et al. 2021

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“…ii) Mitochondrial dysfunction pathway is significantly changed in NFPAs with evidence of upregulation of key molecules [upregulated DEPs: NDUFS8 (NADH ubiquinone oxidoreductase core subunit S8), COX6B (cytochrome c oxidase subunit 6B), CAT (catalase), β-secret2, and ATP5B (ATP synthase, H+ transporting mitochondrial F1 complex, beta subunit)], and downregulation of key molecules [downregulated DEPs: GPX4 (glutathione peroxidase 4), and ATP5A1] in this pathway. Mitochondrial dysfunction can increase ROS production in cancer cells to mediate tumor-related signaling pathways and activate pro-oncogenic signaling ( Li and Zhan, 2019 ). iii) Oxidative phosphorylation pathway is significantly changed in NFPAs with evidence of upregulation of key molecules (upregulated DEPs: NDUFS8, COX6B, and ATP5B) in this pathway.…”

Section: Multiuomics Reveals Oxidative Stress-related Pathway Alteratmentioning

confidence: 99%

“…Mitochondrial oxidative phosphorylation system contains mitochondrial complexes I, II, III, IV, and V, which are the major sites that produce endogenous ROS such as OH . and O − 2 ; among these, complexes I, II, and III play a crucial role in the generation of mitochondrial ROS, because the electrons tend to be leaky at complexes I and III, which results in an incomplete reduction of oxygen and thus generates a free radical such as superoxide radical ( Li and Zhan, 2019 ). iv) Glutathione redox reaction I pathway is significantly changed in NFPAs with evidence of downregulation of key molecule (downregulated DEP: GPX4) in this pathway.…”

Section: Multiuomics Reveals Oxidative Stress-related Pathway Alteratmentioning

confidence: 99%

“…Integrative analysis of these omics data has revealed some important signaling pathway network alterations in PA pathogenesis, including mitochondrial dysfunction, oxidative stress, cell cycle dysregulation, and mitogen-activated protein kinase (MAPK) signaling pathway alteration ( Zhan and Desiderio, 2010a ; Long et al, 2019 ). Mitochondrial dysfunction pathway network and mitochondrial dynamics ( Li and Zhan, 2019 ), and MAPK signaling pathway-based drug therapeutic targets ( Lu et al, 2019 ) have been discussed in detailed in PAs. It is well-known that mitochondria are the energy factories of the body, and mitochondrial metabolism is the source of reactive oxygen species (ROS).…”

Section: Introductionmentioning

confidence: 99%

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Targeting Nrf2-Mediated Oxidative Stress Response Signaling Pathways as New Therapeutic Strategy for Pituitary Adenomas

Zhan

Zhou

2021

Front. Pharmacol.

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Oxidative stress and oxidative damage are the common pathophysiological characteristics in pituitary adenomas (PAs), which have been confirmed with many omics studies in PA tissues and cell/animal experimental studies. Nuclear factor erythroid 2 p45-related factor 2 (Nrf2), the core of oxidative stress response, is an oxidative stress sensor. Nrf2 is synthesized and regulated by multiple factors, including Keap1, ERK1/2, ERK5, JNK1/2, p38 MAPK, PKC, PI3K/AKT, and ER stress, in the cytoplasm. Under the oxidative stress status, Nrf2 quickly translocates from cytoplasm into the nucleus and binds to antioxidant response element /electrophile responsive element to initiate the expressions of antioxidant genes, phases I and II metabolizing enzymes, phase III detoxifying genes, chaperone/stress response genes, and ubiquitination/proteasomal degradation proteins. Many Nrf2 or Keap1 inhibitors have been reported as potential anticancer agents for different cancers. However, Nrf2 inhibitors have not been studied as potential anticancer agents for PAs. We recommend the emphasis on in-depth studies of Nrf2 signaling and potential therapeutic agents targeting Nrf2 signaling pathways as new therapeutic strategies for PAs. Also, the use of Nrf2 inhibitors targeting Nrf2 signaling in combination with ERK inhibitors plus p38 activators or JNK activators targeting MAPK signaling pathways, or drugs targeting mitochondrial dysfunction pathway might produce better anti-tumor effects on PAs. This perspective article reviews the advances in oxidative stress and Nrf2-mediated oxidative stress response signaling pathways in pituitary tumorigenesis, and the potential of targeting Nrf2 signaling pathways as a new therapeutic strategy for PAs.

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“…TMZ resistance is a major obstacle in GBM treatment. Changes in mitochondrial function may affect the sensitivity of GBM cells to TMZ (25,26). We hypothesized that the IMD-or anti-IMD antibody-induced changes in the expression of respiratory chain complex I subunits may affect the toxicity of TMZ.…”

Section: Imd Is Involved In Mitochondrial Function and Hypoxia-inducementioning

confidence: 99%

Inhibition of Intermedin (Adrenomedullin 2) Suppresses the Growth of Glioblastoma and Increases the Antitumor Activity of Temozolomide

Huang

Wang

Feng

et al. 2021

Molecular Cancer Therapeutics

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Glioblastoma multiforme (GBM; grade IV glioma) is the most malignant type of primary brain tumor and is characterized by rapid proliferation and invasive growth. Intermedin (IMD) is an endogenous peptide belonging to the calcitonin gene-related peptide family and has been reported to play an important role in cell survival and invasiveness in several types of cancers. In this study, we found that the expression level of IMD was positively related to the malignancy grade of gliomas. The highest expression of IMD was found in GBM, indicating that IMD may play an important role in glioma malignancy. IMD increased the invasive ability of glioma cells by promoting filopodia formation, which is dependent on ERK1/2 activation. IMD-induced ERK1/2 phosphorylation also promoted GBM cell proliferation. In addition, IMD enhanced mitochondrial function and hypoxia-induced responses in GBM cells. Treatment with anti-IMD monoclonal antibodies not only inhibited tumor growth in both ectopic and orthotopic models of GBM but also significantly enhanced the antitumor activity of temozolomide. Our study may provide novel insights into the mechanism of GBM cell invasion and proliferation and provide an effective strategy to improve the therapeutic effect of GBM treatments.

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Mitochondrial Dysfunction Pathway Networks and Mitochondrial Dynamics in the Pathogenesis of Pituitary Adenomas

Cited by 29 publications

References 142 publications

The crosstalk between HIFs and mitochondrial dysfunctions in cancer development

The crosstalk between HIFs and mitochondrial dysfunctions in cancer development

Targeting Nrf2-Mediated Oxidative Stress Response Signaling Pathways as New Therapeutic Strategy for Pituitary Adenomas

Inhibition of Intermedin (Adrenomedullin 2) Suppresses the Growth of Glioblastoma and Increases the Antitumor Activity of Temozolomide

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