Untangling the Metabolic Reprogramming in Brain Cancer: Discovering Key Molecular Players Using Mass Spectrometry

2019 ◽  
Vol 19 (17) ◽  
pp. 1521-1534 ◽  
Author(s):  
Anatoly Sorokin ◽  
Vsevolod Shurkhay ◽  
Stanislav Pekov ◽  
Evgeny Zhvansky ◽  
Daniil Ivanov ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Brain Cancer ◽  
De Novo ◽  
Aerobic Glycolysis ◽  
Lipid Production ◽  
Dietary Fatty Acids ◽  
Metabolic Reprogramming ◽  
Detection Methods ◽  
Malignant Cells ◽  
Proliferating Cells

Cells metabolism alteration is the new hallmark of cancer, as well as an important method for carcinogenesis investigation. It is well known that the malignant cells switch to aerobic glycolysis pathway occurring also in healthy proliferating cells. Recently, it was shown that in malignant cells de novo synthesis of the intracellular fatty acid replaces dietary fatty acids which change the lipid composition of cancer cells noticeably. These alterations in energy metabolism and structural lipid production explain the high proliferation rate of malignant tissues. However, metabolic reprogramming affects not only lipid metabolism but many of the metabolic pathways in the cell. 2-hydroxyglutarate was considered as cancer cell biomarker and its presence is associated with oxidative stress influencing the mitochondria functions. Among the variety of metabolite detection methods, mass spectrometry stands out as the most effective method for simultaneous identification and quantification of the metabolites. As the metabolic reprogramming is tightly connected with epigenetics and signaling modifications, the evaluation of metabolite alterations in cells is a promising approach to investigate the carcinogenesis which is necessary for improving current diagnostic capabilities and therapeutic capabilities. In this paper, we overview recent studies on metabolic alteration and oncometabolites, especially concerning brain cancer and mass spectrometry approaches which are now in use for the investigation of the metabolic pathway.

scholarly journals Phytochemicals Block Glucose Utilization and Lipid Synthesis to Counteract Metabolic Reprogramming in Cancer Cells

2021 ◽  
Vol 11 (3) ◽  
pp. 1259
Author(s):  
Qiong Wu ◽  
Bo Zhao ◽  
Guangchao Sui ◽  
Jinming Shi
Keyword(s):  
Cancer Cells ◽  
Metabolic Pathways ◽  
De Novo ◽  
Aerobic Glycolysis ◽  
Structural Characteristics ◽  
Natural Compounds ◽  
Metabolic Reprogramming ◽  
De Novo Lipogenesis ◽  
Anticancer Activities ◽  
Substrate Analogs

Aberrant metabolism is one of the hallmarks of cancers. The contributions of dysregulated metabolism to cancer development, such as tumor cell survival, metastasis and drug resistance, have been extensively characterized. “Reprogrammed” metabolic pathways in cancer cells are mainly represented by excessive glucose consumption and hyperactive de novo lipogenesis. Natural compounds with anticancer activities are constantly being demonstrated to target metabolic processes, such as glucose transport, aerobic glycolysis, fatty acid synthesis and desaturation. However, their molecular targets and underlying anticancer mechanisms remain largely unclear or controversial. Mounting evidence indicated that these natural compounds could modulate the expression of key regulatory enzymes in various metabolic pathways at transcriptional and translational levels. Meanwhile, natural compounds could also inhibit the activities of these enzymes by acting as substrate analogs or altering their protein conformations. The actions of natural compounds in the crosstalk between metabolism modulation and cancer cell destiny have become increasingly attractive. In this review, we summarize the activities of natural small molecules in inhibiting key enzymes of metabolic pathways. We illustrate the structural characteristics of these compounds at the molecular level as either inhibitor of various enzymes or regulators of metabolic pathways in cancer cells. Our ultimate goal is to both facilitate the clinical application of natural compounds in cancer therapies and promote the development of novel anticancer therapeutics.

scholarly journals Assimilation and turnover rates of lipid compounds in dominant Antarctic copepods fed with 13 C-enriched diatoms

2020 ◽  
Vol 375 (1804) ◽  
pp. 20190647 ◽  
Author(s):  
Martin Graeve ◽  
Lauris Boissonnot ◽  
Barbara Niehoff ◽  
Wilhelm Hagen ◽  
Gerhard Kattner
Keyword(s):  
Fatty Acids ◽  
Total Lipid ◽  
De Novo ◽  
Lipid Production ◽  
Isotope Analysis ◽  
Dietary Fatty Acids ◽  
Total Lipids ◽  
Turnover Rates ◽  
High Turnover ◽  
Fatty Acids And Alcohols

The study revealed species- and stage-specific differences in lipid accumulation of the dominant Antarctic copepods, the primarily herbivorous Calanoides acutus (copepodite stage V (CV), females) and the more omnivorous Calanus propinquus (females) storing wax esters and triacylglycerols, respectively, which were collected in summer (end of December). Feeding carbon-labelled diatoms to these copepods, 13 C elucidated assimilation and turnover rates of copepod total lipids as well as specific fatty acids and alcohols. The 13 C incorporation was monitored by compound-specific stable isotope analysis (CSIA). CV stages of C. acutus exhibited an intense total lipid turnover and 55% of total lipids were labelled after 9 days of feeding. By contrast, total lipid assimilation of female C. acutus and C. propinquus was lower with 29% and 32%, respectively. The major dietary fatty acids 16:0, 16:1(n − 7) and 20:5(n − 3) had high turnover rates in all specimens. In C. acutus CV, the high rates of the de novo synthesized long-chain monounsaturated fatty acids and alcohols 20:1(n − 9) and 22:1(n − 11) indicate intense lipid deposition, whereas these rates were low in females. The differences in lipid assimilation and turnover clearly show that the copepod species exhibit a high variability and plasticity to adapt their lipid production to their various life phases. This article is part of the theme issue ‘The next horizons for lipids as ‘trophic biomarkers': evidence and significance of consumer modification of dietary fatty acids'.

scholarly journals Metabolic Reprogramming of Thyroid Cancer Cells and Crosstalk in Their Microenvironment

2021 ◽  
Vol 11 ◽  
Author(s):  
Lisha Bao ◽  
Tong Xu ◽  
Xixuan Lu ◽  
Ping Huang ◽  
Zongfu Pan ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Cancer Cells ◽  
Tumor Cells ◽  
De Novo ◽  
Aerobic Glycolysis ◽  
Lipid Synthesis ◽  
Acid Synthesis ◽  
Tumor Formation ◽  
Metabolic Reprogramming ◽  
Normal Cells

Metabolism differs significantly between tumor and normal cells. Metabolic reprogramming in cancer cells and metabolic interplay in the tumor microenvironment (TME) are important for tumor formation and progression. Tumor cells show changes in both catabolism and anabolism. Altered aerobic glycolysis, known as the Warburg effect, is a well-recognized characteristic of tumor cell energy metabolism. Compared with normal cells, tumor cells consume more glucose and glutamine. The enhanced anabolism in tumor cells includes de novo lipid synthesis as well as protein and nucleic acid synthesis. Although these forms of energy supply are uneconomical, they are required for the functioning of cancer cells, including those in thyroid cancer (TC). Increasing attention has recently focused on alterations of the TME. Understanding the metabolic changes governing the intricate relationship between TC cells and the TME may provide novel ideas for the treatment of TC.

scholarly journals Glycolysis and glutaminolysis cooperatively control T cell function by limiting metabolite supply to N-glycosylation

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Lindsey Araujo ◽  
Phillip Khim ◽  
Haik Mkhikian ◽  
Christie-Lynn Mortales ◽  
Michael Demetriou
Keyword(s):  
T Cell ◽  
Biosynthetic Pathway ◽  
Cell Function ◽  
De Novo ◽  
Aerobic Glycolysis ◽  
Proliferating Cells ◽  
Metabolic Switch ◽  
Hexosamine Biosynthetic Pathway ◽  
Otto Warburg ◽  
Hexosamine Pathway

Rapidly proliferating cells switch from oxidative phosphorylation to aerobic glycolysis plus glutaminolysis, markedly increasing glucose and glutamine catabolism. Although Otto Warburg first described aerobic glycolysis in cancer cells >90 years ago, the primary purpose of this metabolic switch remains controversial. The hexosamine biosynthetic pathway requires glucose and glutamine for de novo synthesis of UDP-GlcNAc, a sugar-nucleotide that inhibits receptor endocytosis and signaling by promoting N-acetylglucosamine branching of Asn (N)-linked glycans. Here, we report that aerobic glycolysis and glutaminolysis co-operatively reduce UDP-GlcNAc biosynthesis and N-glycan branching in mouse T cell blasts by starving the hexosamine pathway of glucose and glutamine. This drives growth and pro-inflammatory TH17 over anti-inflammatory-induced T regulatory (iTreg) differentiation, the latter by promoting endocytic loss of IL-2 receptor-α (CD25). Thus, a primary function of aerobic glycolysis and glutaminolysis is to co-operatively limit metabolite supply to N-glycan biosynthesis, an activity with widespread implications for autoimmunity and cancer.

scholarly journals Can small molecular inhibitors that stop de novo serine synthesis be used in cancer treatment?

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Megan Jessica McNamee ◽  
David Michod ◽  
Maria Victoria Niklison-Chirou
Keyword(s):  
Cancer Treatment ◽  
De Novo ◽  
Selective Inhibition ◽  
Metabolic Reprogramming ◽  
Current Status ◽  
Metabolic Processes ◽  
Proliferating Cells ◽  
Growth And Survival ◽  
Cancer Breast ◽  
Small Molecular Inhibitors

AbstractTo sustain their malignancy, tumour cells acquire several metabolic adaptations such as increased oxygen, glucose, glutamine, and lipids uptake. Other metabolic processes are also enhanced as part of tumour metabolic reprogramming, for example, increased serine metabolism. Serine is a non-essential amino acid that supports several metabolic processes that are crucial for the growth and survival of proliferating cells, including protein, DNA, and glutathione synthesis. Indeed, increased activity of D-3-phosphoglycerate dehydrogenase (PHGDH), the enzyme rate-limiting de novo serine synthesis, has been extensively reported in several tumours. Therefore, selective inhibition of PHGDH may represent a new therapeutic strategy for over-expressing PHGDH tumours, owing to its downstream inhibition of essential biomass production such as one-carbon units and nucleotides. This perspective article will discuss the current status of research into small molecular inhibitors against PHGDH in colorectal cancer, breast cancer, and Ewing’s sarcoma. We will summarise recent studies on the development of PHGDH-inhibitors, highlighting their clinical potential as new therapeutics. It also wants to shed a light on some of the key limitations of the use of PHGDH-inhibitors in cancer treatment which are worth taking into account.

Algorithm Development of de novo Peptide Sequencing Via Tandem Mass Spectrometry

2011 ◽  
Vol 37 (12) ◽  
pp. 1278-1288 ◽  
Author(s):  
Han-Chang SUN ◽  
Ji-Yang ZHANG ◽  
Hui LIU ◽  
Wei ZHANG ◽  
Chang-Ming XU ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Tandem Mass Spectrometry ◽  
De Novo ◽  
Peptide Sequencing ◽  
Tandem Mass ◽  
Algorithm Development

scholarly journals Metabolic Anti-Cancer Effects of Melatonin: Clinically Relevant Prospects

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 3018
Author(s):  
Marek Samec ◽  
Alena Liskova ◽  
Lenka Koklesova ◽  
Kevin Zhai ◽  
Elizabeth Varghese ◽  
...  
Keyword(s):  
Cancer Metabolism ◽  
Glucose Transporter ◽  
Aerobic Glycolysis ◽  
Cell Metabolism ◽  
Lactate Production ◽  
Pentose Phosphate ◽  
Metabolic Reprogramming ◽  
Effective Prevention ◽  
Anti Cancer ◽  
Glucose 6 Phosphate Dehydrogenase

Metabolic reprogramming characterized by alterations in nutrient uptake and critical molecular pathways associated with cancer cell metabolism represents a fundamental process of malignant transformation. Melatonin (N-acetyl-5-methoxytryptamine) is a hormone secreted by the pineal gland. Melatonin primarily regulates circadian rhythms but also exerts anti-inflammatory, anti-depressant, antioxidant and anti-tumor activities. Concerning cancer metabolism, melatonin displays significant anticancer effects via the regulation of key components of aerobic glycolysis, gluconeogenesis, the pentose phosphate pathway (PPP) and lipid metabolism. Melatonin treatment affects glucose transporter (GLUT) expression, glucose-6-phosphate dehydrogenase (G6PDH) activity, lactate production and other metabolic contributors. Moreover, melatonin modulates critical players in cancer development, such as HIF-1 and p53. Taken together, melatonin has notable anti-cancer effects at malignancy initiation, progression and metastasing. Further investigations of melatonin impacts relevant for cancer metabolism are expected to create innovative approaches supportive for the effective prevention and targeted therapy of cancers.

scholarly journals AAV-Mediated CRISPRi and RNAi Based Gene Silencing in Mouse Hippocampal Neurons

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 324
Author(s):  
Matthias Deutsch ◽  
Anne Günther ◽  
Rodrigo Lerchundi ◽  
Christine R. Rose ◽  
Sabine Balfanz ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Initiation ◽  
Hippocampal Neurons ◽  
De Novo ◽  
Protein Biosynthesis ◽  
Physiological Role ◽  
High Specificity ◽  
Hcn Channels ◽  
Proliferating Cells ◽  
Neuronal Tissues

Uncovering the physiological role of individual proteins that are part of the intricate process of cellular signaling is often a complex and challenging task. A straightforward strategy of studying a protein’s function is by manipulating the expression rate of its gene. In recent years, the Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)/Cas9-based technology was established as a powerful gene-editing tool for generating sequence specific changes in proliferating cells. However, obtaining homogeneous populations of transgenic post-mitotic neurons by CRISPR/Cas9 turned out to be challenging. These constraints can be partially overcome by CRISPR interference (CRISPRi), which mediates the inhibition of gene expression by competing with the transcription machinery for promoter binding and, thus, transcription initiation. Notably, CRISPR/Cas is only one of several described approaches for the manipulation of gene expression. Here, we targeted neurons with recombinant Adeno-associated viruses to induce either CRISPRi or RNA interference (RNAi), a well-established method for impairing de novo protein biosynthesis by using cellular regulatory mechanisms that induce the degradation of pre-existing mRNA. We specifically targeted hyperpolarization-activated and cyclic nucleotide-gated (HCN) channels, which are widely expressed in neuronal tissues and play essential physiological roles in maintaining biophysical characteristics in neurons. Both of the strategies reduced the expression levels of three HCN isoforms (HCN1, 2, and 4) with high specificity. Furthermore, detailed analysis revealed that the knock-down of just a single HCN isoform (HCN4) in hippocampal neurons did not affect basic electrical parameters of transduced neurons, whereas substantial changes emerged in HCN-current specific properties.

scholarly journals Identifying molecules as biosignatures with assembly theory and mass spectrometry

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Stuart M. Marshall ◽  
Cole Mathis ◽  
Emma Carrick ◽  
Graham Keenan ◽  
Geoffrey J. T. Cooper ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
De Novo ◽  
Outer Space ◽  
Molecular Assembly ◽  
Detection Experiment ◽  
Complex Molecules ◽  
The World ◽  
Life Detection ◽  
Molecular Complexity ◽  
The Universe

AbstractThe search for alien life is hard because we do not know what signatures are unique to life. We show why complex molecules found in high abundance are universal biosignatures and demonstrate the first intrinsic experimentally tractable measure of molecular complexity, called the molecular assembly index (MA). To do this we calculate the complexity of several million molecules and validate that their complexity can be experimentally determined by mass spectrometry. This approach allows us to identify molecular biosignatures from a set of diverse samples from around the world, outer space, and the laboratory, demonstrating it is possible to build a life detection experiment based on MA that could be deployed to extraterrestrial locations, and used as a complexity scale to quantify constraints needed to direct prebiotically plausible processes in the laboratory. Such an approach is vital for finding life elsewhere in the universe or creating de-novo life in the lab.

scholarly journals The fatty acid receptor CD36 promotes HCC progression through activating Src/PI3K/AKT axis-dependent aerobic glycolysis

2021 ◽  
Vol 12 (4) ◽  
Author(s):  
Xiaoqing Luo ◽  
Enze Zheng ◽  
Li Wei ◽  
Han Zeng ◽  
Hong Qin ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Aerobic Glycolysis ◽  
Lactic Acid Production ◽  
Metabolic Reprogramming ◽  
Metabolic Phenotype ◽  
Hepatic Tissue ◽  
Promoting Effect ◽  
Acid Receptor ◽  
Hcc Cells ◽  
Fatty Acid Receptor

AbstractMetabolic reprogramming is a new hallmark of cancer but it remains poorly defined in hepatocellular carcinogenesis (HCC). The fatty acid receptor CD36 is associated with both lipid and glucose metabolism in the liver. However, the role of CD36 in metabolic reprogramming in the progression of HCC still remains to be elucidated. In the present study, we found that CD36 is highly expressed in human HCC as compared with non-tumor hepatic tissue. CD36 overexpression promoted the proliferation, migration, invasion, and in vivo tumor growth of HCC cells, whereas silencing CD36 had the opposite effects. By analysis of cell metabolic phenotype, CD36 expression showed a positive association with extracellular acidification rate, a measure of glycolysis, instead of oxygen consumption rate. Further experiments verified that overexpression of CD36 resulted in increased glycolysis flux and lactic acid production. Mechanistically, CD36 induced mTOR-mediated oncogenic glycolysis via activation of Src/PI3K/AKT signaling axis. Pretreatment of HCC cells with PI3K/AKT/mTOR inhibitors largely blocked the tumor-promoting effect of CD36. Our findings suggest that CD36 exerts a stimulatory effect on HCC growth and metastasis, through mediating aerobic glycolysis by the Src/PI3K/AKT/mTOR signaling pathway.

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