Metabolic reprogramming and disease progression in cancer patients

Torresano, Laura; Nuevo‐Tapioles, Cristina; Santacatterina, Fulvio; Cuezva, José M.

doi:10.1016/j.bbadis.2020.165721

Cited by 53 publications

(56 citation statements)

References 234 publications

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“…Cancer metabolic reprogramming is believed to hold a great potential as a source of novel biomarkers and molecular targets for chemoprevention and treatment [ 5 ]. Altered concentration of L-arginine/NO pathway metabolites at systemic level and their utility as diagnostic and prognostic tools in CRC has already been demonstrated [ 7 ].…”

Section: Discussionmentioning

confidence: 99%

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L-Arginine/Nitric Oxide Pathway Is Altered in Colorectal Cancer and Can Be Modulated by Novel Derivatives from Oxicam Class of Non-Steroidal Anti-Inflammatory Drugs

Krzystek−Korpacka

Szczęśniak-Sięga

Szczuka

et al. 2020

Cancers

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L-arginine/nitric oxide pathway metabolites are altered in colorectal cancer (CRC). We evaluated underlying changes in pathway enzymes in 55 paired tumor/tumor-adjacent samples and 20 normal mucosa using quantitative-PCR and assessed the impact of classic and novel oxicam analogues on enzyme expression and intracellular metabolite concentration (LC-MS/MS) in Caco-2, HCT116, and HT-29 cells. Compared to normal mucosa, ARG1, PRMT1, and PRMT5 were overexpressed in both tumor and tumor-adjacent tissue and DDAH2 solely in tumor-adjacent tissue. Tumor-adjacent tissue had higher expression of ARG1, DDAH1, and DDAH2 and lower NOS2 than patients-matched tumors. The ARG1 expression in tumors increased along with tumor grade and reflected lymph node involvement. Novel oxicam analogues with arylpiperazine moiety at the thiazine ring were more effective in downregulating DDAHs and PRMTs and upregulating ARG2 than piroxicam and meloxicam. An analogue distinguished by propylene linker between thiazine’s and piperazine’s nitrogen atoms and containing two fluorine substituents was the strongest inhibitor of DDAHs and PRMTs expression, while an analogue containing propylene linker but no fluorine substituents was the strongest inhibitor of ARG2 expression. Metabolic reprogramming in CRC includes overexpression of DDAHs and PRMTs in addition to ARG1 and NOS2 and is not restricted to tumor tissue but can be modulated by novel oxicam analogues.

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Section: Discussionmentioning

confidence: 99%

“…However, cancer metabolism is highly flexible and cancer type- and context-dependent [ 4 ]. Therefore, further research employing quantitative metabolic profiling is needed to translate metabolic abnormalities into clinical practice successfully [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

L-Arginine/Nitric Oxide Pathway Is Altered in Colorectal Cancer and Can Be Modulated by Novel Derivatives from Oxicam Class of Non-Steroidal Anti-Inflammatory Drugs

Krzystek−Korpacka

Szczęśniak-Sięga

Szczuka

et al. 2020

Cancers

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“…Most of these are redundant with stresses already mentioned above, but in cancer these can often occur in combination, leading to greater deviations from normal cell physiology and larger impacts on S metabolism. Metabolic realignments in transformed cells, such as the preferential switch to glycolysis, are often associated with increased levels of ROS in these cells, which, in turn, is expected to increase their reliance on the disulfide reductase-based antioxidant systems (63,128). Conditions of hypoxia, nutrient restriction, or inflammation within the tumor microenvironment can further increase metabolic and oxidative stresses.…”

Section: Figmentioning

confidence: 99%

Sulfur Metabolism Under Stress

Miller

Schmidt

2020

Antioxidants & Redox Signaling

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Significance: In humans, imbalances in the reduction-oxidation (redox) status of cells are associated with many pathological states. In addition, many therapeutics and prophylactics used as interventions for diverse pathologies either directly modulate oxidant levels or otherwise influence endogenous cellular redox systems. Recent Advances: The cellular machineries that maintain redox homeostasis or that function within antioxidant defense systems rely heavily on the regulated reactivities of sulfur atoms either within or derived from the amino acids cysteine and methionine. Recent advances have substantially advanced our understanding of the complex and essential chemistry of biological sulfur-containing molecules. Critical Issues: The redox machineries that maintain cellular homeostasis under diverse stresses can consume large amounts of energy to generate reducing power and/or large amounts of sulfur-containing nutrients to replenish or sustain intracellular stores. By understanding the metabolic pathways underlying these responses, one can better predict how to protect cells from specific stresses. Future Directions: Here, we summarize the current state of knowledge about the impacts of different stresses on cellular metabolism of sulfur-containing molecules. This analysis suggests that there remains more to be learned about how cells use sulfur chemistry to respond to stresses, which could in turn lead to advances in therapeutic interventions for some exposures or conditions.

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“…More and more evidences show that the metabolic pattern of cell carcinogenesis has changed significantly, which involves many aspects such as glycolysis, TCA cycle, oxidative phosphorylation, amino acid metabolism, fatty acid metabolism and nucleic acid metabolism (3). This phenomenon is known as the metabolic reprogramming of tumor cells (4).…”

Section: Introductionmentioning

confidence: 99%

Comprehensive Analysis of Prognostic Markers for Acute Myeloid Leukemia Based on Four Metabolic Genes

Zhang

Wang

et al. 2020

Front. Oncol.

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Background: Metabolic reprogramming is the core characteristic of tumors during the development of tumors, and cancer cells can rely on metabolic changes to support their rapid growth. Nevertheless, an overall analysis of metabolic markers in acute myeloid leukemia (AML) is absent and urgently needed. Methods: Within this work, genetic expression, mutation data and clinical data of AML were queried from Genotype-Tissue Expression (GTEx) database, The Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) database. The tumor samples of TCGA were randomly divided into a training group (64 samples) and an internal validation group (64 samples) at one time, and the tumor samples of GEO served as two external validation groups (99 samples, 374 samples). According to the expression levels of survival-associated metabolic genes, we divided all TCGA tumor samples into high, medium and low metabolism groups, and evaluated the immune cell activity in the tumor microenvironment of the three metabolism groups by single-sample gene set enrichment analysis (ssGSEA) algorithm. Finally, we examined the mutations and prognostic effects of each model gene. Results: Four metabolism-related genes were screened and applied to construct a prognostic model for AML, giving excellent results. As for the area under the curve (AUC) value of receiver operating characteristic (ROC) curve, the training group was up to 0.902 (1-year), 0.81 (3-year), and 0.877 (5-year); and the internal and external validation groups also met the expected standards, showing high potency in predicting patient outcome. Univariate and multivariate prognostic analyses indicated that the riskScore obtained from our prognostic model was an independent prognostic factor. ssGSEA analysis revealed the high metabolism group had higher immune activity. Single and multiple gene survival analysis validated that each model gene had significant effects on the overall survival of AML patients. Conclusions: In our study, a high-efficiency prognostic prediction model was built and validated for AML patients. The results showed that metabolism-related genes could become potential prognostic biomarkers for AML.

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Metabolic reprogramming and disease progression in cancer patients

Cited by 53 publications

References 234 publications

L-Arginine/Nitric Oxide Pathway Is Altered in Colorectal Cancer and Can Be Modulated by Novel Derivatives from Oxicam Class of Non-Steroidal Anti-Inflammatory Drugs

L-Arginine/Nitric Oxide Pathway Is Altered in Colorectal Cancer and Can Be Modulated by Novel Derivatives from Oxicam Class of Non-Steroidal Anti-Inflammatory Drugs

Sulfur Metabolism Under Stress

Comprehensive Analysis of Prognostic Markers for Acute Myeloid Leukemia Based on Four Metabolic Genes

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