Increased formate overflow is a hallmark of oxidative cancer

Meiser, Johannes; Schuster, Anne; Pietzke, Matthias; Voorde, Johan Vande; Athineos, Dimitris; Oizel, Kristell; Burgos-Barragan, Guillermo; Wit, Niek J. de; Dhayade, Sandeep; Morton, Jennifer P.; Dornier, Emmanuel; Sumpton, David; Mackay, Gillian; Blyth, Karen; Patel, Ketan; Niclou, Simone P.; Vazquez, Alexei

doi:10.1038/s41467-018-03777-w

Cited by 96 publications

(146 citation statements)

References 29 publications

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“…6B). We also showed that the transformed tissues have a high NAD + /(NAD + +NADH) ratio that is either similar than the normal tissue (Meiser et al, 2018) (Fig. 6C).…”

Section: In Vivo Validation In Mouse Models Of Cancermentioning

confidence: 61%

“…To this end we utilized a combination of 13 C-Methanol tracing, quantification of metabolites by LC-MS and metabolic flux analysis. We showed that the relative rate of serine catabolism to formate was increased in the transformed tissues relative to the normal tissues (Meiser et al, 2018) (Fig. 6B).…”

Section: In Vivo Validation In Mouse Models Of Cancermentioning

confidence: 85%

“…Both pathways can sustain the one-carbon demands of cell proliferation, but the mitochondrial pathway is essential for the manifestation of formate overflow (Bao et al, 2016;Ducker et al, 2016;Meiser et al, 2016). We have also shown that the catabolism of serine to formate is increased in tumours of genetically engineered mouse models of cancer resulting in an increase of serum formate levels (Meiser et al, 2018). Yet, it remains an open question what the role is of excess formate production by mitochondrial serine catabolism.…”

Section: Introductionmentioning

confidence: 85%

“…6A). We have previously performed a metabolic characterization of tissues from the APC min/+ mouse model of colorectal adenomas and the MMTV-PyMT model of breast adenocarcinoma (Meiser et al, 2018). To this end we utilized a combination of 13 C-Methanol tracing, quantification of metabolites by LC-MS and metabolic flux analysis.…”

Section: In Vivo Validation In Mouse Models Of Cancermentioning

confidence: 99%

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Formate induces a metabolic switch in nucleotide and energy metabolism

Oizel

Tait-Mulder

Fernández-de-Cossio-Díaz

et al. 2019

Preprint

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Formate is a precursor for the de novo synthesis of purine and deoxythymidine nucleotides. Formate also interacts with energy metabolism by promoting the synthesis of adenine nucleotides. Here we use theoretical modelling together with metabolomics analysis to investigate the link between formate, nucleotide and energy metabolism. We uncover that endogenous or exogenous formate induces a metabolic switch from low to high adenine nucleotide levels, increasing the rate of glycolysis and repressing the AMPK activity. Formate also induces an increase in the pyrimidine precursor orotate and the urea cycle intermediate argininosuccinate, in agreement with the ATP dependent activities of carbamoyl-phosphate and argininosuccinate synthetase. In vivo data for mouse and human cancers confirms the association between increased formate production, nucleotide and energy metabolism. Finally, the in vitro observations are recapitulated in mice following intraperitoneal injection of formate. We conclude that formate is a potent regulator of purine, pyrimidine and energy metabolism.

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“…6B). We also showed that the transformed tissues have a high NAD + /(NAD + +NADH) ratio that is either similar than the normal tissue (Meiser et al, 2018) (Fig. 6C).…”

Section: In Vivo Validation In Mouse Models Of Cancermentioning

confidence: 61%

Section: In Vivo Validation In Mouse Models Of Cancermentioning

confidence: 85%

Section: Introductionmentioning

confidence: 85%

Section: In Vivo Validation In Mouse Models Of Cancermentioning

confidence: 99%

See 2 more Smart Citations

Formate induces a metabolic switch in nucleotide and energy metabolism

Oizel

Tait-Mulder

Fernández-de-Cossio-Díaz

et al. 2019

Preprint

Self Cite

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“…For instance, since overflow metabolism is commonly characteristic to both cancer and stem cells, our theory will contribute to understanding the origin of cancer stem cells (38). We also expect that the metabolic behaviours characteristic to cancer such as serine and glycine metabolism (39,40) and the metabolic responses to drugs (23) will be understood by the microeconomics of metabolism.…”

Section: R a F Tmentioning

confidence: 96%

Microeconomics of metabolism: Overflow metabolism as Giffen behaviour

Yamagishi

Hatakeyama

2019

Preprint

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Biological systems such as intracellular metabolism are rationally regulated to maximize the cellular growth rate through evolution (1-4), whereas microeconomics investigates the behaviour of consumers assumed to rationally maximize their utility (5,6). Despite this analogy as optimization problems, the link between biology and economics has not been fully established (7,8). Here, we developed an exact mapping between the regulation of metabolism and the theory of consumer choice, thereby revealing the correspondence between long-standing mysteries in both fields: overflow metabolism and Giffen behaviour. Overflow metabolism, particularly known as the Warburg effect in cancer (9, 10), is a seemingly wasteful but ubiquitous strategy where cells utilize aerobic glycolysis instead of the more energetically-efficient oxidative phosphorylation (9-16), whereas Giffen behaviour is the unexpected consumer behaviour where a good is demanded more as its price rises (17,18). We revealed that the general conditions for these phenomena are trade-off and complementarity, i.e., impossibility of substitution for different goods. This correspondence implies that oxidative phosphorylation is counterintuitively stimulated when its efficiency is decreased by metabolic perturbations like drug administration. Therefore, Giffen behaviour bridges the Warburg effect and the reverse and inverse Warburg effect (19)(20)(21)(22). This highlights that application of microeconomics to metabolism can offer new predictions and paradigms for both biology and economics. metabolic systems | theory of consumer choice | Warburg effect | optimization | trade-off Correspondence: hatakeyama@complex.c.u-tokyo.ac.jp Yamagishi et al. | bioR‰iv | February 29, 2020 | 1-5

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Tumor‐On‐A‐Chip Model Incorporating Human‐Based Hydrogels for Easy Assessment of Metastatic Tumor Inter‐Heterogeneity

Monteiro,

Deus,

Silva

et al. 2024

Adv Funct Materials

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The coordinated migration of invasive tumor cells is a complex and dynamic mechanism driven by diverse cellular and molecular events. Unfortunately, the inherent heterogeneity within tumors raises multiple challenges in deciphering key biomarkers and novel therapeutic approaches to prevent tumor metastasis. Here, a microengineered tumor‐on‐a‐chip system incorporating human platelet lysate hydrogels is proposed to recreate the early metastatic process of tumor invasion and drug response. By co‐culturing human bone marrow mesenchymal stem cells with two tumor cell lines with distinct metastatic capability, the developed model can emulate the 3D tumor microarchitecture and inter‐heterogeneity regarding its intrinsic metastatic ability. The recreated microenvironment supports tumor and stromal cell movement, evidencing the synergistic tumor‐stromal cell and cell‐extracellular matrix interactions of an invading tumor. Through gene and protein expression analysis and exometabolomic profiling, this tumor‐on‐a‐chip platform provides evidence for the role of a dynamic environment as a key regulator of tumor metastatic ability. Additionally, the effect of doxorubicin treatment on tumor invasiveness and biomarker profile highlights the suitability of the established models for therapy assessment. Overall, this study presents a tumor‐on‐a‐chip model useful to pursue mechanistic studies on early metastatic events in a fully human‐derived microenvironment, while contributing with fundamental insights into biomolecular profiling.

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Increased formate overflow is a hallmark of oxidative cancer

Cited by 96 publications

References 29 publications

Formate induces a metabolic switch in nucleotide and energy metabolism

Formate induces a metabolic switch in nucleotide and energy metabolism

Microeconomics of metabolism: Overflow metabolism as Giffen behaviour

Tumor‐On‐A‐Chip Model Incorporating Human‐Based Hydrogels for Easy Assessment of Metastatic Tumor Inter‐Heterogeneity

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