Metabolic Remodeling as a Way of Adapting to Tumor Microenvironment (TME), a Job of Several Holders

Serpa, Jacinta

doi:10.1007/978-3-030-34025-4_1

Cited by 21 publications

(27 citation statements)

References 394 publications

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“…As a nitrogen source, glutamine is used as a substrate for nucleotide (purines, pyrimidines, and amino sugars) and nicotinamide adenine dinucleotide phosphate (NADPH) synthesis [ 14 ]. As a carbon source, glutamine supplies the tricarboxylic acid (TCA) cycle with oxaloacetate, α-ketoglutarate, and acetyl-CoA, thus being responsible for ATP and macromolecules synthesis, preferentially replacing glucose in certain tumors [ 15 , 16 , 17 ]. Furthermore, glutamine is a precursor of glutamate, which is necessary for the synthesis of non-essential amino acids and glutathione (GSH), the most important reactive oxygen species (ROS) scavenger and detoxifying agent [ 18 , 19 ].…”

Section: Glutamine and Glutamate Metabolism In The Central Nervousmentioning

confidence: 99%

Take Advantage of Glutamine Anaplerosis, the Kernel of the Metabolic Rewiring in Malignant Gliomas

et al. 2020

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Glutamine is a non-essential amino acid that plays a key role in the metabolism of proliferating cells including neoplastic cells. In the central nervous system (CNS), glutamine metabolism is particularly relevant, because the glutamine-glutamate cycle is a way of controlling the production of glutamate-derived neurotransmitters by tightly regulating the bioavailability of the amino acids in a neuron-astrocyte metabolic symbiosis-dependent manner. Glutamine-related metabolic adjustments have been reported in several CNS malignancies including malignant gliomas that are considered ‘glutamine addicted’. In these tumors, glutamine becomes an essential amino acid preferentially used in energy and biomass production including glutathione (GSH) generation, which is crucial in oxidative stress control. Therefore, in this review, we will highlight the metabolic remodeling that gliomas undergo, focusing on glutamine metabolism. We will address some therapeutic regimens including novel research attempts to target glutamine metabolism and a brief update of diagnosis strategies that take advantage of this altered profile. A better understanding of malignant glioma cell metabolism will help in the identification of new molecular targets and the design of new therapies.

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Section: Glutamine and Glutamate Metabolism In The Central Nervousmentioning

confidence: 99%

Take Advantage of Glutamine Anaplerosis, the Kernel of the Metabolic Rewiring in Malignant Gliomas

et al. 2020

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“…Cancer cells overexpressing xCT present an overactivation of the glucose-dependent PPP, as a mean of replacing NADPH consumed in the imperative conversion of cystine into cysteine ( 76 ). Furthermore, xCT makes a bridge between cysteine uptake and glutamine metabolism, since glutamine is the main precursor of glutamate, whose export is essential for xCT-mediated import of cysteine ( 17 ). The role of xCT, as a facilitator of cyst(e)ine protective antioxidant role in cancer cells, is evidenced by the regulation of its expression by Nrf2 ( 111 ) and by signaling pathways activated by oxidative stress, including PI3K/AKT/mTOR ( 56 , 112 , 113 ) and MAPK pathways ( 110 ).…”

Section: Regulators and Mediators Of Cysteine Transport In Cancermentioning

confidence: 99%

“…Cysteine and glutathione are crucial in the maintenance of the metabolic course ( 10 – 13 ), since the cancer metabolic rewiring implies the generation of oxidative stress ( 14 – 16 ). Nevertheless, cysteine has been underestimated as a carbon source, due to the core position of glycolysis in the cellular biosynthesis and bioenergetics, being major emphasis given to glucose as a preferential fuel and to glutamine as its main substitute [as reviewed in ( 17 , 18 )].…”

Section: Introductionmentioning

confidence: 99%

Cysteine as a Carbon Source, a Hot Spot in Cancer Cells Survival

Serpa

2020

Front. Oncol.

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Cancer cells undergo a metabolic rewiring in order to fulfill the energy and biomass requirements. Cysteine is a pivotal organic compound that contributes for cancer metabolic remodeling at three different levels: (1) in redox control, free or as a component of glutathione; (2) in ATP production, via hydrogen sulfide (H 2 S) production, serving as a donor to electron transport chain (ETC), and (3) as a carbon source for biomass and energy production. In the present review, emphasis will be given to the role of cysteine as a carbon source, focusing on the metabolic reliance on cysteine, benefiting the metabolic fitness and survival of cancer cells. Therefore, the interplay between cysteine metabolism and other metabolic pathways, as well as the regulation of cysteine metabolism related enzymes and transporters, will be also addressed. Finally, the usefulness of cysteine metabolic route as a target in cancer treatment will be highlighted.

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“…In fact, a high rate of glycolysis followed by lactic acid production, the Warburg effect, is a common feature of cancer cells. However, cancer cells do not completely abrogate OXPHOS [ 1 , 150 , 151 , 152 , 153 ], but rather fulfil OXPHOS mainly using other substrates besides glucose, such as lactate, fatty acids and glutamine [ 154 ]. Therefore, the increased rate of glycolysis in cancer aims to supply other glucose dependent pathways to sustain biomass production and cell proliferation, as the pentose phosphate pathway [ 154 , 155 ].…”

Section: Role Of the Cat:mst Axis In Cancer Metabolic Remodelingmentioning

confidence: 99%

Cysteine Aminotransferase (CAT): A Pivotal Sponsor in Metabolic Remodeling and an Ally of 3-Mercaptopyruvate Sulfurtransferase (MST) in Cancer

Hipólito

Nunes

Vicente³

et al. 2020

Molecules

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Metabolic remodeling is a critical skill of malignant cells, allowing their survival and spread. The metabolic dynamics and adaptation capacity of cancer cells allow them to escape from damaging stimuli, including breakage or cross-links in DNA strands and increased reactive oxygen species (ROS) levels, promoting resistance to currently available therapies, such as alkylating or oxidative agents. Therefore, it is essential to understand how metabolic pathways and the corresponding enzymatic systems can impact on tumor behavior. Cysteine aminotransferase (CAT) per se, as well as a component of the CAT: 3-mercaptopyruvate sulfurtransferase (MST) axis, is pivotal for this metabolic rewiring, constituting a central mechanism in amino acid metabolism and fulfilling the metabolic needs of cancer cells, thereby supplying other different pathways. In this review, we explore the current state-of-art on CAT function and its role on cancer cell metabolic rewiring as MST partner, and its relevance in cancer cells’ fitness.

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Metabolic Remodeling as a Way of Adapting to Tumor Microenvironment (TME), a Job of Several Holders

Cited by 21 publications

References 394 publications

Take Advantage of Glutamine Anaplerosis, the Kernel of the Metabolic Rewiring in Malignant Gliomas

Take Advantage of Glutamine Anaplerosis, the Kernel of the Metabolic Rewiring in Malignant Gliomas

Cysteine as a Carbon Source, a Hot Spot in Cancer Cells Survival

Cysteine Aminotransferase (CAT): A Pivotal Sponsor in Metabolic Remodeling and an Ally of 3-Mercaptopyruvate Sulfurtransferase (MST) in Cancer

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