The hallmarks of cancer metabolism: Still emerging

Cell Metabolism, Journal Year: 2022, Volume and Issue: 34(3), P. 355 - 377

Published: Feb. 4, 2022

Language: Английский

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Hypoxia-inducible factors: cancer progression and clinical translation

Journal of Clinical Investigation, Journal Year: 2022, Volume and Issue: 132(11)

Published: May 31, 2022

Hypoxia-inducible factors (HIFs) are master regulators of oxygen homeostasis that match O2 supply and demand for each the 50 trillion cells in adult human body. Cancer co-opt this homeostatic system to drive cancer progression. HIFs activate transcription thousands genes mediate angiogenesis, stem cell specification, motility, epithelial-mesenchymal transition, extracellular matrix remodeling, glucose lipid metabolism, immune evasion, invasion, metastasis. In Review, mechanisms consequences HIF activation presented. The current status future prospects small-molecule inhibitors use as therapeutics discussed.

Language: Английский

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The effect of HIF on metabolism and immunity

Nature Reviews Nephrology, Journal Year: 2022, Volume and Issue: 18(9), P. 573 - 587

Published: June 20, 2022

Language: Английский

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Redox regulation of the immune response

Cellular and Molecular Immunology, Journal Year: 2022, Volume and Issue: 19(10), P. 1079 - 1101

Published: Sept. 2, 2022

Abstract The immune-inflammatory response is associated with increased nitro-oxidative stress. aim of this mechanistic review to examine: (a) the role redox-sensitive transcription factors and enzymes, ROS/RNS production, activity cellular antioxidants in activation performance macrophages, dendritic cells, neutrophils, T-cells, B-cells, natural killer cells; (b) involvement high-density lipoprotein (HDL), apolipoprotein A1 (ApoA1), paraoxonase-1 (PON1), oxidized phospholipids regulating immune response; (c) detrimental effects hypernitrosylation chronic stress on response. redox changes during responses are orchestrated by actions nuclear factor-κB, HIF1α, target rapamycin, phosphatidylinositol 3-kinase/protein kinase B signaling pathway, mitogen-activated protein kinases, 5' AMP-activated kinase, peroxisome proliferator-activated receptor. survival individual cells under control depends intracellular extracellular levels ROS/RNS. They heavily influenced including glutathione thioredoxin systems, factor erythroid 2-related 2, HDL/ApoA1/PON1 complex. Chronic inhibit those antioxidant tricarboxylic acid cycle, mitochondrial functions, metabolism cells. In conclusion, redox-associated mechanisms modulate metabolic reprogramming macrophage T helper cell polarization, phagocytosis, production pro- versus anti-inflammatory cytokines, training tolerance, chemotaxis, pathogen sensing, antiviral antibacterial effects, Toll-like receptor activity, endotoxin tolerance.

Language: Английский

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Role of LDH in tumor glycolysis: Regulation of LDHA by small molecules for cancer therapeutics

Seminars in Cancer Biology, Journal Year: 2022, Volume and Issue: 87, P. 184 - 195

Published: Nov. 9, 2022

Language: Английский

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Modulating Glycolysis to Improve Cancer Therapy

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(3), P. 2606 - 2606

Published: Jan. 30, 2023

Cancer cells undergo metabolic reprogramming and switch to a ‘glycolysis-dominant’ profile promote their survival meet requirements for energy macromolecules. This phenomenon, also known as the ‘Warburg effect,’ provides advantage cancer make tumor environment more pro-cancerous. Additionally, increased glycolytic dependence promotes chemo/radio resistance. A similar is shown by immune in microenvironment, inducing competition between tumor-infiltrating over nutrients. Several recent studies have that targeting enhanced glycolysis promising strategy them susceptible treatment with other conventional modalities, including chemotherapy, radiotherapy, hormonal therapy, immunotherapy, photodynamic therapy. Although several strategies been developed of are different stages pre-clinical clinical evaluation, there still lack effective specifically target cell improve efficacy. Herein, we reviewed our current understanding role how this phenomenon could be potential efficacy

Language: Английский

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Pathophysiological mechanisms and therapeutic approaches in obstructive sleep apnea syndrome

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: May 25, 2023

Abstract Obstructive sleep apnea syndrome (OSAS) is a common breathing disorder in which the airways narrow or collapse during sleep, causing obstructive apnea. The prevalence of OSAS continues to rise worldwide, particularly middle-aged and elderly individuals. mechanism upper airway incompletely understood but associated with several factors, including obesity, craniofacial changes, altered muscle function airway, pharyngeal neuropathy, fluid shifts neck. main characteristics are recurrent pauses respiration, lead intermittent hypoxia (IH) hypercapnia, accompanied by blood oxygen desaturation arousal sharply increases risk diseases. This paper first briefly describes epidemiology, incidence, pathophysiological mechanisms OSAS. Next, alterations relevant signaling pathways induced IH systematically reviewed discussed. For example, can induce gut microbiota (GM) dysbiosis, impair intestinal barrier, alter metabolites. These ultimately secondary oxidative stress, systemic inflammation, sympathetic activation. We then summarize effects on disease pathogenesis, cardiocerebrovascular disorders, neurological metabolic diseases, cancer, reproductive COVID-19. Finally, different therapeutic strategies for caused causes proposed. Multidisciplinary approaches shared decision-making necessary successful treatment future, more randomized controlled trials needed further evaluation define what treatments best specific patients.

Language: Английский

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Mitochondrial complex I ROS production and redox signaling in hypoxia

Redox Biology, Journal Year: 2023, Volume and Issue: 67, P. 102926 - 102926

Published: Oct. 16, 2023

Mitochondria are a main source of cellular energy. Oxidative phosphorylation (OXPHOS) is the major process aerobic respiration. Enzyme complexes electron transport chain (ETC) pump protons to generate protonmotive force (Δp) that drives OXPHOS. Complex I an entry point into ETC. oxidizes nicotinamide adenine dinucleotide (NADH) and transfers electrons ubiquinone in reaction coupled with proton pumping. also produces reactive oxygen species (ROS) under various conditions. The enzymatic activities complex can be regulated by metabolic conditions serves as regulatory node ROS plays diverse roles cell metabolism ranging from physiologic pathologic Progress our understanding indicates release important signaling functions. Increasing evidence suggests mismatch energy production demand. In this article, we review role sensing acute hypoxia.

Language: Английский

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Transition of acute kidney injury to chronic kidney disease: role of metabolic reprogramming

Metabolism, Journal Year: 2022, Volume and Issue: 131, P. 155194 - 155194

Published: March 26, 2022

Language: Английский

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Metabolic reprogramming and epigenetic modifications in cancer: from the impacts and mechanisms to the treatment potential

Experimental & Molecular Medicine, Journal Year: 2023, Volume and Issue: 55(7), P. 1357 - 1370

Published: July 3, 2023

Abstract Metabolic reprogramming and epigenetic modifications are hallmarks of cancer cells. In cells, metabolic pathway activity varies during tumorigenesis progression, indicating regulated plasticity. changes often closely related to changes, such as alterations in the expression or epigenetically modified enzymes, which may exert a direct an indirect influence on cellular metabolism. Therefore, exploring mechanisms underlying regulating tumor cell metabolism is important for further understanding pathogenesis. Here, we mainly focus latest studies regulations, including glucose, lipid amino acid context, then emphasize modifications. Specifically, discuss role played by DNA methylation, chromatin remodeling, noncoding RNAs histone lactylation growth progression. Finally, summarize prospects potential therapeutic strategies based

Language: Английский

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