New frontiers in metabolomics: from measurement to insight

Riekeberg, Eli; Powers, Robert

doi:10.12688/f1000research.11495.1

Cited by 118 publications

(90 citation statements)

References 83 publications

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“…Accumulation of MMA results from increased flux through and/or deregulation of the enzymes in this pathway and is a marker for a group of inborn metabolic diseases called methylmalonic acidemias, as well as of vitamin B12 deficiency 26 . Large-scale exploratory metabolomic experiments are notorious for their lack of sensitivity and quantitation 27 ; therefore, to gain a deeper insight into the dynamics of MMA levels with age we determined the absolute concentration of this metabolite in the sera samples from all 60 donors. This deeper analysis revealed a more substantial increase in the levels of MMA in the sera of the old μ M) compared to the young donors (0.1-1.5 μ M) ( Fig.…”

Section: Discussionmentioning

confidence: 99%

Age-induced methylmalonic acid accumulation promotes tumor progression and aggressiveness

Gomes

Ilter

Low

et al. 2020

Preprint

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From age 65 onwards, the risk of cancer incidence and associated mortality is substantially higher 1-3 . Nonetheless, our understanding of the complex relationship between age and cancer is still in its infancy 4 . For decades, the link has largely been attributed to increased exposure time to mutagens in older individuals. However, this view does not account for the wellestablished role of diet, exercise and small molecules that target the pace of metabolic aging [5][6][7][8] . Here, we show that metabolic alterations that occur with age can render a systemic environment favorable to progression and aggressiveness of tumors. Specifically, we show that methylmalonic acid (MMA), a by-product of propionate metabolism, is significantly up-regulated in the serum of older people, and functions as a mediator of tumor progression. We traced this to the induction of SOX4 and a consequent transcriptional reprogramming that can endow cancer cells with aggressive properties. Thus, accumulation of MMA represents a novel link between aging and cancer progression, implicating MMA as a novel therapeutic target for advanced carcinomas.It has long been known that age is one of the main risk factors for cancer incidence [9][10][11] . How it contributes to cancer progression, however, is not well understood 2,3,12 . Considering the growing body of evidence demonstrating that cancer cell-extrinsic factors are key in modulating tumor progression, we hypothesized that aging produces a systemic environment that supports tumor progression and development of aggressive properties. To test this hypothesis, we cultured A549 non-small cell lung cancer (NSCLC) and HCC1806 triple negative breast cancer (TNBC) cells in 10% human serum from 30 young (age ≤ 30) and 30 old (age ≥ 60) individuals with no diagnosed disease ( Fig. 1a; Extended Data Table 1). While the majority of cells treated with young donor sera maintained their epithelial morphology (25 out of 30), cells treated with 25 out of the 30 old donor sera became mesenchymal, losing polarity and displaying a spindle-shaped morphology (Extended Data Fig. 1-3). These phenotypes were independent of donor ethnicity, and resembled epithelial-to-mesenchymal transition (EMT), a developmental process that during cancer pathogenesis can confer cells the cellular plasticity necessary to acquire proaggressive and pro-metastatic properties 13 . Cells cultured in the presence of sera from aged donors displayed a pronounced loss of the epithelial marker E-cadherin and gain of the mesenchymal markers fibronectin and vimentin 13 , in addition to increased expression of SERPINE1 and MMP2 14,15 -proteins highly associated with aggressive phenotypes (Fig. 1b, Extended Data Fig. 4a, b). Moreover, the aged sera promoted resistance to two distinct and widely used chemotherapeutic drugs, carboplatin and paclitaxel (Fig. 1c, Extended Data Fig. 4c). Compelled by these observations, we questioned if the cells treated with the old donor sera would also display heightened metastatic potential. We treated MDA-MB-2...

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Section: Discussionmentioning

confidence: 99%

Age-induced methylmalonic acid accumulation promotes tumor progression and aggressiveness

Gomes

Ilter

Low

et al. 2020

Preprint

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“…Another future direction is the incorporation of the whole spectrum of “omics” technologies, ie, transcriptomics, proteomics, and metabolomics in radio‐“omics” research. It can be expected that the integration of multiple “omics” technologies—genomics, transcriptomics, proteomics, metabolomics—with advanced imaging techniques will further open up new avenues in the diagnosis and treatment of diseases, with initial data being promising …”

Section: Future Directionsmentioning

confidence: 99%

Background, current role, and potential applications of radiogenomics

Pinker

Shitano

Sala

et al. 2017

Magnetic Resonance Imaging

158

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“…high-throughput next-generation sequencing, mass spectrometry-based flow cytometry or real-time molecular imaging) will generate new information but, at the same time, massive amounts of (big) data that will have to be adequately handled, analysed and interpreted [112][113][114]. In this context, RIEKEBERG and POWERS [115] recently reviewed the methodological advancements and successful applications of metabolomics, one the newest omic fields.…”

Section: Technical Challengesmentioning

confidence: 99%

From systems biology to P4 medicine: applications in respiratory medicine

2018

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Human health and disease are emergent properties of a complex, nonlinear, dynamic multilevel biological system: the human body. Systems biology is a comprehensive research strategy that has the potential to understand these emergent properties holistically. It stems from advancements in medical diagnostics, "omics" data and bioinformatic computing power. It paves the way forward towards "P4 medicine" ( predictive, preventive, personalised and participatory), which seeks to better intervene preventively to preserve health or therapeutically to cure diseases. In this review, we: 1) discuss the principles of systems biology; 2) elaborate on how P4 medicine has the potential to shift healthcare from reactive medicine (treatment of illness) to predict and prevent illness, in a revolution that will be personalised in nature, probabilistic in essence and participatory driven; 3) review the current state of the art of network (systems) medicine in three prevalent respiratory diseases (chronic obstructive pulmonary disease, asthma and lung cancer); and 4) outline current challenges and future goals in the field.

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New frontiers in metabolomics: from measurement to insight

Cited by 118 publications

References 83 publications

Age-induced methylmalonic acid accumulation promotes tumor progression and aggressiveness

Age-induced methylmalonic acid accumulation promotes tumor progression and aggressiveness

Background, current role, and potential applications of radiogenomics

From systems biology to P4 medicine: applications in respiratory medicine

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