CPT1A-mediated Fat Oxidation, Mechanisms, and Therapeutic Potential

Endocrinology, Journal Year: 2020, Volume and Issue: 161(2)

Published: Jan. 4, 2020

Abstract Energy homeostasis during fasting or prolonged exercise depends on mitochondrial fatty acid oxidation (FAO). This pathway is crucial in many tissues with high energy demand and its disruption results inborn FAO deficiencies. More than 15 genetic defects have been currently described, pathological variants described circumpolar populations provide insights into critical role metabolism. The use of acids as requires more 2 dozen enzymes transport proteins, which are involved the activation mitochondria. As key rate-limiting enzyme FAO, carnitine palmitoyltransferase I (CPT1) regulates facilitates adaptation to environment, both health disease, including cancer. CPT1 family proteins contains 3 isoforms: CPT1A, CPT1B, CPT1C. review focuses liver isoform that catalyzes step converting acyl-coenzyme acyl-carnitines, can then cross membranes get regulation CPT1A complex has several layers involve genetic, epigenetic, physiological, nutritional modulators. It ubiquitously expressed body associated dire consequences linked mutations, metabolic disorders, cancers. makes an attractive target for therapeutic interventions. discusses our current understanding expression, heath potential opportunities targeting this enzyme.

Language: Английский

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NADPH homeostasis in cancer: functions, mechanisms and therapeutic implications

Signal Transduction and Targeted Therapy, Journal Year: 2020, Volume and Issue: 5(1)

Published: Oct. 7, 2020

Abstract Nicotinamide adenine dinucleotide phosphate (NADPH) is an essential electron donor in all organisms, and provides the reducing power for anabolic reactions redox balance. NADPH homeostasis regulated by varied signaling pathways several metabolic enzymes that undergo adaptive alteration cancer cells. The reprogramming of renders cells both highly dependent on this network antioxidant capacity more susceptible to oxidative stress. Modulating unique might be effective strategy eliminate these In review, we summarize current existing literatures homeostasis, including its biological functions, regulatory mechanisms corresponding therapeutic interventions human cancers, providing insights into implications targeting metabolism associated mechanism therapy.

Language: Английский

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The Evasion Mechanisms of Cancer Immunity and Drug Intervention in the Tumor Microenvironment

Frontiers in Pharmacology, Journal Year: 2022, Volume and Issue: 13

Published: May 24, 2022

Recently, in the field of cancer treatment, paradigm has changed to immunotherapy that activates immune system induce attacks. Among them, checkpoint inhibitors (ICI) are attracting attention as excellent and continuous clinical results. However, it shows not only limitations such efficacy some patients or indications, but also side-effects resistance occur. Therefore, is necessary understand factors tumor microenvironment (TME) affect immunotherapy, is, mechanism by which grows while evading suppressing attacks from within TME. Tumors can evade through various mechanisms restricting antigen recognition, inhibiting system, inducing T cell exhaustion. In addition, tumors inhibit accumulating specific metabolites signal TME limiting nutrients available cells. order overcome develop effective treatments therapeutic strategies, an approach needed functions cells integrated manner based on this review, we will examine effects cells, especially how anti-cancer strategies

Language: Английский

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Metabolic interventions in the immune response to cancer

Nature reviews. Immunology, Journal Year: 2019, Volume and Issue: 19(5), P. 324 - 335

Published: Feb. 28, 2019

Language: Английский

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Adipocyte extracellular vesicles carry enzymes and fatty acids that stimulate mitochondrial metabolism and remodeling in tumor cells

The EMBO Journal, Journal Year: 2020, Volume and Issue: 39(3)

Published: Jan. 10, 2020

Language: Английский

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STAT proteins in cancer: orchestration of metabolism

Nature reviews. Cancer, Journal Year: 2023, Volume and Issue: 23(3), P. 115 - 134

Published: Jan. 3, 2023

Language: Английский

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Malignant Ascites in Ovarian Cancer: Cellular, Acellular, and Biophysical Determinants of Molecular Characteristics and Therapy Response

Cancers, Journal Year: 2021, Volume and Issue: 13(17), P. 4318 - 4318

Published: Aug. 26, 2021

Ascites refers to the abnormal accumulation of fluid in peritoneum resulting from an underlying pathology, such as metastatic cancer. Among all cancers, advanced-stage epithelial ovarian cancer is most frequently associated with production malignant ascites and leading cause death gynecologic malignancies. Despite decades evidence showing that peritoneal portends poorest outcomes for patients, role promoting metastasis therapy resistance remains poorly understood. This review summarizes current understanding ascites, a focus on The first section provides overview heterogeneity pathophysiology ascites. Next, analytical methods used characterize cellular acellular components well these modulating cell biology, are discussed. then perspective pressures forces tumors subjected presence impact physical stress resistance. Treatment options including surgical, pharmacological photochemical interventions discussed highlight challenges opportunities at interface drug discovery, device development sciences oncology.

Language: Английский

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Lipid metabolism alteration contributes to and maintains the properties of cancer stem cells

Theranostics, Journal Year: 2020, Volume and Issue: 10(16), P. 7053 - 7069

Published: Jan. 1, 2020

Lipids, the basic components of cell membrane, execute fundamental roles in almost all activities including cell-cell recognition, signalling transduction and energy supplies.Lipid metabolism is elementary for life sustentation that balances activity between synthesis degradation.An accumulating amount data has indicated abnormal lipid cancer stem cells (CSCs), alteration exerts a great impact on CSCs' properties such as capability self-renewal, differentiation, invasion, metastasis, drug sensitivity resistance.CSCs' formation maintenance cannot do without regulation fatty acids cholesterol.In normal embryonic development, cholesterol are regulated by some important pathways (such Hedgehog, Notch, Wnt pathways); these also play crucial initiating and/or maintaining properties, shown to be commonly modulated CSCs; other hand, altered turn modifies generates additional impacts CSCs.Metabolic rewiring considered an ideal hallmark CSCs, metabolic alterations would promising therapeutic targets CSCs aggressive tumors.In this review, we summarize most updated findings abnormalities prospect potential applications targeting anticancer treatment.

Language: Английский

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Lipid Metabolism and Resistance to Anticancer Treatment

Biology, Journal Year: 2020, Volume and Issue: 9(12), P. 474 - 474

Published: Dec. 16, 2020

Metabolic reprogramming is crucial to respond cancer cell requirements during tumor development. In the last decade, metabolic alterations have been shown modulate cells’ sensitivity chemotherapeutic agents including conventional and targeted therapies. Recently, it became apparent that changes in lipid metabolism represent important mediators of resistance anticancer agents. this review, we highlight associated with therapy resistance, their significance how dysregulated could be exploited overcome drug resistance.

Language: Английский

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ER stress sensor, glucose regulatory protein 78 (GRP78) regulates redox status in pancreatic cancer thereby maintaining “stemness”

Cell Death and Disease, Journal Year: 2019, Volume and Issue: 10(2)

Published: Feb. 12, 2019

Abstract Endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) signaling have been shown to be dysregulated in multiple cancer types. Glucose regulatory 78 (GRP78), master regulator of UPR, plays a role proliferation, invasion, metastasis cancer. Cancer stem cells (CSCs) make up crucial component tumor heterogeneity pancreatic cancer, as well other cancers. “Stemness” defines population within that increased therapeutic resistance survival advantage. In current study, we investigated how GRP78 was responsible for maintaining “stemness” thereby contributing its aggressive biology. We determined downregulation decreased clonogenicity self-renewal properties cell lines vitro. vivo studies resulted delayed initiation frequency, smaller volume shGRP78 groups. Additionally, fatty acid metabolism tumors cells. Further, our results showed dysregulates transcriptomic proteomic pathways involve DNA damage, oxidative stress, death, were reversed upon treatment with ROS inhibitor, N-acetylcysteine. This study thus demonstrates first time heightened UPR may maintenance these are attributed like chemoresistance metastasis.

Language: Английский

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