Arginine Signaling and Cancer Metabolism

Chen, Chialin; Hsu, Sheng Chieh; Ann, David K.; Yen, Yun; Kung, Hsing Jien

doi:10.3390/cancers13143541

Cited by 121 publications

(94 citation statements)

References 167 publications

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“…By mTOR mediation, Arg thus has profound impacts on protein synthesis, lipid synthesis and nucleotide synthesis of cancer cells ( Ban et al, 2004 ; Saxton & Sabatini, 2017 ). In addition, Arg can also bind G-protein coupled receptor to activate down-stream RAS/ERK or PI3K pathway, another essential pathway in cancer development and progression ( Chen et al, 2021 ). Therefore, as the building blocks of Arg biosynthetic pathway, Asp, Orn and Cit might be signaling metabolites and act as transcriptome reprogrammer in cancer metabolism.…”

Section: Discussionmentioning

confidence: 99%

Changes in serum amino acid levels in non-small cell lung cancer: a case-control study in Chinese population

Liu

Long

Wang

et al. 2022

PeerJ

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Background Previous studies have shown the alteration of amino acid (AA) profile in patients with non-small cell lung cancer (NSCLC). However, there is little data regarding AA profile in NSCLC in Chinese population. The aim of this study was to evaluate AA profile in Chinese NSCLC patients, explore its utility in sample classification and further discuss its related metabolic pathways. Methods The concentrations of 22 AAs in serum samples from 200 patients with NSCLC and 202 healthy controls were determined by liquid chromatography-tandem mass spectrometer (LC-MS/MS). AA levels in different tumor stages and histological types were also discussed. The performance of AA panel in classifying the cases and controls was evaluated in the training data set and validation data set based on the receiver operating characteristic (ROC) curve, and the important metabolic pathways were identified. Results The concentrations of tryptophan (Trp), phenylalanine (Phe), isoleucine (Ile), glycine (Gly), serine (Ser), aspartic acid (Asp), asparagine (Asn), cystein (Cys), glutamic acid (Glu), ornithine (Orn) and citrulline (Cit) were significantly altered in NSCLC patients compared with controls (all P-FDR < 0.05). Among these, four AAs including Asp, Cys, Glu and Orn were substantially up-regulated in NSCLC patients (FC ≥ 1.2). AA levels were significantly altered in patients with late-stage NSCLC, but not in those with early-stage when comparing with healthy controls. In terms of histological type, these AAs were altered in both adenocarcinoma and squamous cell carcinoma. For discrimination of NSCLC from controls, the area under the ROC curve (AUC) was 0.80 (95% CI [0.74–0.85]) in the training data set and 0.79 (95%CI [0.71–0.87]) in the validation data set. The AUCs for early-stage and late-stage NSCLC were 0.75 (95% CI [0.68–0.81]) and 0.86 (95% CI [0.82–0.91]), respectively. Moreover, the model showed a better performance in the classification of squamous cell carcinoma (AUC = 0.90, 95% CI [0.85–0.95]) than adenocarcinoma (AUC = 0.77, 95% CI [0.71–0.82]) from controls. Three important metabolic pathways were involved in the alteration of AA profile, including Gly, Ser and Thr metabolism; Ala, Asp and Glu metabolism; and Arg biosynthesis. Conclusions The levels of several AAs in serum were altered in Chinese NSCLC patients. These altered AAs may be utilized to classify the cases from the controls. Gly, Ser and Thr metabolism; Ala, Asp and Glu metabolism and Arg biosynthesis pathways may play roles in metabolism of the NSCLC patient.

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Section: Discussionmentioning

confidence: 99%

Changes in serum amino acid levels in non-small cell lung cancer: a case-control study in Chinese population

Liu

Long

Wang

et al. 2022

PeerJ

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“…Metabolic alterations along the Arg/ADMA pathway may provide useful biomarkers for CRC tumour progression in future studies. Interestingly, Arg is the most consumed amino acid in the inner necrotic core of tumour mass [75]. There is also some evidence that elevated ADMA levels influence the depth of tumour invasion and poor clinical outcomes in gastric cancer samples [76].…”

Section: Discussionmentioning

confidence: 99%

Changing Metabolic Patterns along the Colorectal Adenoma–Carcinoma Sequence

Tevini

Eder

Huber-Schönauer

et al. 2022

JCM

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Colorectal cancer (CRC) is a major public health burden and one of the leading causes of cancer-related deaths worldwide. Screening programs facilitate early diagnosis and can help to reduce poor outcomes. Serum metabolomics can extract vital molecular information that may increase the sensitivity and specificity of colonoscopy in combination with histopathological examination. The present study identifies serum metabolite patterns of treatment-naïve patients, diagnosed with either advanced adenoma (AA) or CRC in colonoscopy screenings, in the framework of the SAKKOPI (Salzburg Colon Cancer Prevention Initiative) program. We used a targeted flow injection analysis and liquid chromatography-tandem mass spectrometry metabolomics approach (FIA- and LC-MS/MS) to characterise the serum metabolomes of an initial screening cohort and two validation cohorts (in total 66 CRC, 76 AA and 93 controls). The lipidome was significantly perturbed, with a proportion of lipid species being downregulated in CRC patients, as compared to AA and controls. The predominant alterations observed were in the levels of lyso-lipids, glycerophosphocholines and acylcarnitines, but additionally, variations in the quantity of hydroxylated sphingolipids could be detected. Changed amino acid metabolism was restricted mainly to metabolites of the arginine/dimethylarginine/NO synthase pathway. The identified metabolic divergences observed in CRC set the foundation for mechanistic studies to characterise biochemical pathways that become deregulated during progression through the adenoma to carcinoma sequence and highlight the key importance of lipid metabolites. Biomarkers related to these pathways could improve the sensitivity and specificity of diagnosis, as well as the monitoring of therapies.

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“…Arginine [ 147 ] plays a critical role in regulating T cell activity and immune responses [ 148 ]. Arginine can be found in the TIME, and its levels are depleted in tumors [ 149 ].…”

Section: Combination Therapy: Icb and Metabolismmentioning

confidence: 99%

New Immunometabolic Strategy Based on Cell Type-Specific Metabolic Reprogramming in the Tumor Immune Microenvironment

Sung

Cheong

2022

Cells

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Immunometabolism is an emerging discipline in cancer immunotherapy. Tumor tissues are heterogeneous and influenced by metabolic reprogramming of the tumor immune microenvironment (TIME). In the TIME, multiple cell types interact, and the tumor and immune cells compete for limited nutrients, resulting in altered anticancer immunity. Therefore, metabolic reprogramming of individual cell types may influence the outcomes of immunotherapy. Understanding the metabolic competition for access to limited nutrients between tumor cells and immune cells could reveal the breadth and complexity of the TIME and aid in developing novel therapeutic approaches for cancer. In this review, we highlight that, when cells compete for nutrients, the prevailing cell type gains certain advantages over other cell types; for instance, if tumor cells prevail against immune cells for nutrients, the former gains immune resistance. Thus, a strategy is needed to selectively suppress such resistant tumor cells. Although challenging, the concept of cell type-specific metabolic pathway inhibition is a potent new strategy in anticancer immunotherapy.

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Arginine Signaling and Cancer Metabolism

Cited by 121 publications

References 167 publications

Changes in serum amino acid levels in non-small cell lung cancer: a case-control study in Chinese population

Changes in serum amino acid levels in non-small cell lung cancer: a case-control study in Chinese population

Changing Metabolic Patterns along the Colorectal Adenoma–Carcinoma Sequence

New Immunometabolic Strategy Based on Cell Type-Specific Metabolic Reprogramming in the Tumor Immune Microenvironment

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