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

Serpa, Jacinta

doi:10.3389/fonc.2020.00947

Cited by 39 publications

(38 citation statements)

References 140 publications

(157 reference statements)

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“…Cysteine is used by cancer cells as a carbon source, with increased cysteine bioavailability acting as a stimulus for metabolic reprogramming. When there is no limit on cysteine uptake, its contribution to cell growth and proliferation mainly occurs through cysteine catabolism [ 137 ]. Cysteine catabolism results in the production of organic compounds, such as pyruvate, α-glutarate, α-ketobutyrate, serine, propionyl-CoA, succinate, and acetyl-CoA to supply the TCA cycle, intermediates for fatty acid and protein synthesis, and hydrogen sulfide.…”

Section: Other Neaasmentioning

confidence: 99%

Mechanisms of Metabolic Reprogramming in Cancer Cells Supporting Enhanced Growth and Proliferation

Schiliro

Firestein

2021

Cells

321

152

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Cancer cells alter metabolic processes to sustain their characteristic uncontrolled growth and proliferation. These metabolic alterations include (1) a shift from oxidative phosphorylation to aerobic glycolysis to support the increased need for ATP, (2) increased glutaminolysis for NADPH regeneration, (3) altered flux through the pentose phosphate pathway and the tricarboxylic acid cycle for macromolecule generation, (4) increased lipid uptake, lipogenesis, and cholesterol synthesis, (5) upregulation of one-carbon metabolism for the production of ATP, NADH/NADPH, nucleotides, and glutathione, (6) altered amino acid metabolism, (7) metabolism-based regulation of apoptosis, and (8) the utilization of alternative substrates, such as lactate and acetate. Altered metabolic flux in cancer is controlled by tumor-host cell interactions, key oncogenes, tumor suppressors, and other regulatory molecules, including non-coding RNAs. Changes to metabolic pathways in cancer are dynamic, exhibit plasticity, and are often dependent on the type of tumor and the tumor microenvironment, leading in a shift of thought from the Warburg Effect and the “reverse Warburg Effect” to metabolic plasticity. Understanding the complex nature of altered flux through these multiple pathways in cancer cells can support the development of new therapies.

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Section: Other Neaasmentioning

confidence: 99%

Mechanisms of Metabolic Reprogramming in Cancer Cells Supporting Enhanced Growth and Proliferation

Schiliro

Firestein

2021

Cells

321

152

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“…Notably, in pancreatic cancer cells exhibiting PKM1/2 knockdown, 20% of intracellular pyruvate originated from cysteine (Yu et al, 2019). The contribution of cysteine catabolism to cancer has been extensively reviewed by Serpa (2020).…”

Section: Pathways Leading To Pyruvate But Not Commencing From Glucosementioning

confidence: 99%

From Glucose to Lactate and Transiting Intermediates Through Mitochondria, Bypassing Pyruvate Kinase: Considerations for Cells Exhibiting Dimeric PKM2 or Otherwise Inhibited Kinase Activity

Chinopoulos

2020

Front. Physiol.

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A metabolic hallmark of many cancers is the increase in glucose consumption coupled to excessive lactate production. Mindful that L-lactate originates only from pyruvate, the question arises as to how can this be sustained in those tissues where pyruvate kinase activity is reduced due to dimerization of PKM2 isoform or inhibited by oxidative/nitrosative stress, posttranslational modifications or mutations, all widely reported findings in the very same cells. Hereby 17 pathways connecting glucose to lactate bypassing pyruvate kinase are reviewed, some of which transit through the mitochondrial matrix. An additional 69 converging pathways leading to pyruvate and lactate, but not commencing from glucose, are also examined. The minor production of pyruvate and lactate by glutaminolysis is scrutinized separately. The present review aims to highlight the ways through which L-lactate can still be produced from pyruvate using carbon atoms originating from glucose or other substrates in cells with kinetically impaired pyruvate kinase and underscore the importance of mitochondria in cancer metabolism irrespective of oxidative phosphorylation.

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“…It should be mentioned that a significant reprogramming of the cellular sulfur metabolism (which includes alterations in cysteine catabolism and metabolism, cysteine transport, methionine homeostasis, and many other aspects) occurs in cancer cells [ 48 , 49 ]; the mitochondrial roles of H 2 S in cancer (reviewed in the current article), therefore, should be viewed in this broader context.…”

Section: Hydrogen Sulfide (H 2 S) An Endogenoumentioning

confidence: 99%

“…It will be also interesting to assess whether the increased H 2 S biosynthesis in cancer cells is linked to the well-known global reprogramming of substrate (cysteine, homocysteine) biosynthesis and/or cell uptake in cancer. Clearly, cancer cells undergo a global reprogramming of sulfur metabolism [ 48 , 49 ], and the mechanisms discussed in the current article must be placed into this broader context.…”

Section: Additional Mitochondrial Roles Of H 2 mentioning

confidence: 99%

Hydrogen Sulfide, an Endogenous Stimulator of Mitochondrial Function in Cancer Cells

Szabó

2021

Cells

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Hydrogen sulfide (H2S) has a long history as toxic gas and environmental hazard; inhibition of cytochrome c oxidase (mitochondrial Complex IV) is viewed as a primary mode of its cytotoxic action. However, studies conducted over the last two decades unveiled multiple biological regulatory roles of H2S as an endogenously produced mammalian gaseous transmitter. Cystathionine γ-lyase (CSE), cystathionine β-synthase (CBS) and 3-mercaptopyruvate sulfurtransferase (3-MST) are currently viewed as the principal mammalian H2S-generating enzymes. In contrast to its inhibitory (toxicological) mitochondrial effects, at lower (physiological) concentrations, H2S serves as a stimulator of electron transport in mammalian mitochondria, by acting as an electron donor—with sulfide:quinone oxidoreductase (SQR) being the immediate electron acceptor. The mitochondrial roles of H2S are significant in various cancer cells, many of which exhibit high expression and partial mitochondrial localization of various H2S producing enzymes. In addition to the stimulation of mitochondrial ATP production, the roles of endogenous H2S in cancer cells include the maintenance of mitochondrial organization (protection against mitochondrial fission) and the maintenance of mitochondrial DNA repair (via the stimulation of the assembly of mitochondrial DNA repair complexes). The current article overviews the state-of-the-art knowledge regarding the mitochondrial functions of endogenously produced H2S in cancer cells.

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

Cited by 39 publications

References 140 publications

Mechanisms of Metabolic Reprogramming in Cancer Cells Supporting Enhanced Growth and Proliferation

Mechanisms of Metabolic Reprogramming in Cancer Cells Supporting Enhanced Growth and Proliferation

From Glucose to Lactate and Transiting Intermediates Through Mitochondria, Bypassing Pyruvate Kinase: Considerations for Cells Exhibiting Dimeric PKM2 or Otherwise Inhibited Kinase Activity

Hydrogen Sulfide, an Endogenous Stimulator of Mitochondrial Function in Cancer Cells

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