Serine and Metabolism Regulation: A Novel Mechanism in Antitumor Immunity and Senescence

Wu, Qi; Chen, Xinyue; Li, Juanjuan; Sun, Shengrong

doi:10.14336/ad.2020.0314

Cited by 34 publications

(30 citation statements)

References 99 publications

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“…Another example relies to serine (Ser) that is also required in large amount for rapidly growing cells [ 67 – 69 ]. Ser is supplied to cells through uptake from the extracellular environment, and de novo produced by transamination via glycine or from glucose and Glu [ 70 ].…”

Section: Other Amino Acid Metabolism and Signalling Pathwaysmentioning

confidence: 99%

Amino acid metabolism and signalling pathways: potential targets in the control of infection and immunity

Tomé

2021

Eur J Clin Nutr

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Defences to pathogens such as SarCoV2 in mammals involves interactions between immune functions and metabolic pathways to eradicate infection while preventing hyperinflammation. Amino acid metabolic pathways represent with other antimicrobial agent potential targets for therapeutic strategies. iNOS-mediated production of NO from Arg is involved in the innate inflammatory response to pathogens and NO overproduction can induce hyperinflammation. The two Arg-catabolising enzymes Arg1 and IDO1 reduce the hyperinflammation by an immunosuppressive effect via either Arg starvation (for Arg1) or via the immunoregulatory activity of the Arg-derived metabolites Kyn (for IDO1). In response to amino acid abundance mTOR activates the host protein translation and Coronaviruses use this machinery for their own protein synthesis and replication. In contrast GCN2, the sensor of amino acid starvation, activates pathways that restrict inflammation and viral replication. Gln depletion alters the immune response that become more suppressive, by favouring a regulatory T phenotype rather than a Th1 phenotype. Proliferating activated immune cells are highly dependent on Ser, activation and differentiation of T cells need enough Ser and dietary Ser restriction can inhibit their proliferation. Cys is strictly required for T-cell proliferation because they cannot convert Met to Cys. Restricting Met inhibits both viral RNA cap methylation and replication, and the proliferation of infected cells with an increased requirement for Met. Phe catabolism produces antimicrobial metabolites resulting in the inhibition of microbial growth and an immunosuppressive activity towards T lymphocytes.

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Section: Other Amino Acid Metabolism and Signalling Pathwaysmentioning

confidence: 99%

Amino acid metabolism and signalling pathways: potential targets in the control of infection and immunity

Tomé

2021

Eur J Clin Nutr

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“…In this regard, dietary restriction of serine limited T cell responses in a model of L. monocytogenes infection (Ma et al 2017) whilst serine restriction combined with PHGDH knockdown completely prevented T cell proliferation in vitro (Ma et al 2019). The serine, glycine, one-carbon metabolic network enables cells to convert serine and glycine to a number of metabolites that sustain biosynthesis pathways and contribute to redox balance and epigenetic regulation (reviewed in Reina-Campos et al 2020;Wu et al 2020b). The Jones laboratory determined that upregulated expression of serine, glycine, one-carbon pathway enzymes was a feature of activated T cells (Ma et al 2017).…”

Section: Serine and Glycinementioning

confidence: 99%

The Role of Non-essential Amino Acids in T Cell Function and Anti-tumour Immunity

Hope

Salmond

2021

Arch. Immunol. Ther. Exp.

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T cell activation, differentiation and proliferation is dependent upon and intrinsically linked to a capacity to modulate and adapt cellular metabolism. Antigen-induced activation stimulates a transcriptional programme that results in metabolic reprogramming, enabling T cells to fuel anabolic metabolic pathways and provide the nutrients to sustain proliferation and effector responses. Amino acids are key nutrients for T cells and have essential roles as building blocks for protein synthesis as well as in numerous metabolic pathways. In this review, we discuss the roles for uptake and biosynthesis of non-essential amino acids in T cell metabolism, activation and effector function. Furthermore, we highlight the effects of amino acid metabolism and depletion by cancer cells on T cell anti-tumour function and discuss approaches to modulate and improve T cell metabolism for improved anti-tumour function in these nutrient-depleted microenvironments.

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“…Serine and glycine have been found to support oncogenic stimulus in a group of tumors [ 67 , 68 ]. Their role is critical in one-carbon (1C) metabolism [ 71 ], a vital network for different oncogenic mediators.…”

Section: Evidence Of Changes In the Metabolic Pathways Of Tumor Energy Dysfunctionmentioning

confidence: 99%

“…Figure 1 schematizes alterations of amino acid pathways associated with cancer. [67,74,76] Acute myeloid leukemia [75,76] Mesothelioma [64] Lung adenocarcinoma [67] Non-small cell lung cancer [65] Lymphomas [76] Colorectal adenocarcinoma [66] Methotrexate [76,77] Pemetrexed [ [79,81,82] Glutamine deprivation [79] Aminooxyacetate (AOA)…”

Section: Tumors With Altered Amino Acid Metabolismmentioning

confidence: 99%

“…[79] CB-839 [80] BPTES [80] Sulfasalazine [80] V-9302 [80] Compound-968 [83] Sulfonamide sulfonic ester scaffolds [69] Asparagine ASNS [68,84,85] SLC1A5(ASCT-2) [69,86,87] Acute lymphoblastic leukemia [68,84] Adenylated sulfoximine 1 [84] Asparaginase [68] Sulfonamide sulfonic ester scaffolds [69] Serine and glycine have been found to support oncogenic stimulus in a group of tumors [67,68]. Their role is critical in one-carbon (1C) metabolism [71], a vital network for different oncogenic mediators.…”

Section: Tumors With Altered Amino Acid Metabolismmentioning

confidence: 99%

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Metabolic Classification and Intervention Opportunities for Tumor Energy Dysfunction

et al. 2021

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A comprehensive view of cell metabolism provides a new vision of cancer, conceptualized as tissue with cellular-altered metabolism and energetic dysfunction, which can shed light on pathophysiological mechanisms. Cancer is now considered a heterogeneous ecosystem, formed by tumor cells and the microenvironment, which is molecularly, phenotypically, and metabolically reprogrammable. A wealth of evidence confirms metabolic reprogramming activity as the minimum common denominator of cancer, grouping together a wide variety of aberrations that can affect any of the different metabolic pathways involved in cell physiology. This forms the basis for a new proposed classification of cancer according to the altered metabolic pathway(s) and degree of energy dysfunction. Enhanced understanding of the metabolic reprogramming pathways of fatty acids, amino acids, carbohydrates, hypoxia, and acidosis can bring about new therapeutic intervention possibilities from a metabolic perspective of cancer.

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Serine and Metabolism Regulation: A Novel Mechanism in Antitumor Immunity and Senescence

Cited by 34 publications

References 99 publications

Amino acid metabolism and signalling pathways: potential targets in the control of infection and immunity

Amino acid metabolism and signalling pathways: potential targets in the control of infection and immunity

The Role of Non-essential Amino Acids in T Cell Function and Anti-tumour Immunity

Metabolic Classification and Intervention Opportunities for Tumor Energy Dysfunction

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