Metabolic and mind shifts: from glucose to glutamine and acetate addictions in cancer

@article{Corbet2015MetabolicAM,
  title={Metabolic and mind shifts: from glucose to glutamine and acetate addictions in cancer},
  author={Cyril Corbet and Olivier Feron},
  journal={Current Opinion in Clinical Nutrition and Metabolic Care},
  year={2015},
  volume={18},
  pages={346–353}
}
  • C. Corbet, O. Feron
  • Published 1 July 2015
  • Biology, Chemistry
  • Current Opinion in Clinical Nutrition and Metabolic Care
Purpose of reviewGlutamine and acetate were recently identified as alternatives to glucose for fueling the tricarboxylic acid (TCA) cycle in cancer cells, particularly in the context of hypoxia. Recent findingsMolecular mechanisms orchestrating glutamine and acetate metabolism were elicited through the combination of 13C tracer analysis and genetic silencing, or pharmacological modulation of key metabolic enzymes including those converting glutamate into &agr;-ketoglutarate (&agr;KG) (and… 

The Fate of Glutamine in Human Metabolism. The Interplay with Glucose in Proliferating Cells

TLDR
A reduced metabolic model of central carbon and nitrogen metabolism, C2M2N with 77 reactions, 54 internal metabolites, and 3 compartments is developed, taking into account the actual stoichiometry of the reactions, including the stoichiometric role of the cofactors and the irreversibility of some reactions.

The Fate of Glutamine in Human Metabolism. Comparison with Glucose

TLDR
A reduced metabolic model of central carbon metabolism, C2M2 with 63 reactions, 46 internal metabolites and 3 compartments is developed, taking into account the actual stoichiometry of the reactions, including the stoichiometric role of the cofactors and the irreversibility of some reactions.

SLC6A14 and SLC38A5 Drive the Glutaminolysis and Serine–Glycine–One-Carbon Pathways in Cancer

TLDR
SLC6A14 and SLC38A5 are the two transporters that are upregulated in a variety of cancers to mediate the influx of glutamine, serine, glycine, and methionine into cancer cells, and represent novel, hitherto largely unexplored, targets for cancer therapy.

Monocarboxylate transporter 1 promotes proliferation and invasion of renal cancer cells by mediating acetate transport

TLDR
It is revealed that MCT1 is abnormally high in ccRCC and promotes cancer development and the regulatory effect of M CT1 on cell proliferation and invasion maybe mediated by acetate transport.

Molecular Imaging of Metabolic Reprograming in Mutant IDH Cells

TLDR
How metabolic imaging has helped shed light on the basic biology of mutant IDH cells is described, and how this information can be leveraged to identify new therapeutic targets and to develop new clinically translatable imaging methods to detect and monitor Mutant IDH tumors in vivo.

Simultaneous integration of gene expression and nutrient availability for studying metabolism of hepatocellular carcinoma

TLDR
It is shown that the integration of gene expression and nutrient availability data into genome-wide models improves the prediction of metabolic phenotypes.

Simultaneous Integration of Gene Expression and Nutrient Availability for Studying the Metabolism of Hepatocellular Carcinoma Cell Lines

TLDR
It is shown that the integration of gene expression and nutrient availability data into genome-wide models improves the prediction of metabolic phenotypes.

Targeting the Mitochondrial Pyruvate Carrier for Neuroprotection

TLDR
The mechanism and potential feasibility of mitochondrial pyruvate carrier inhibition as a neuroprotective strategy in neuronal injury and neurodegenerative diseases is discussed.

The potential of inhibiting glutamine uptake as a therapeutic target for multiple myeloma

TLDR
Evidence suggests that MM cells acquire a more aggressive phenotype and modify their metabolism to adapt to the hypoxic microenvironment in which they grow, and the interest on the role of Gln metabolism in cancer has steadily increased in the last few years.

References

SHOWING 1-10 OF 38 REFERENCES

Reductive glutamine metabolism by IDH1 mediates lipogenesis under hypoxia

TLDR
It is shown that human cells use reductive metabolism of α-ketoglutarate to synthesize AcCoA for lipid synthesis and support lipid synthesis in mammalian cells.

Glutamine supports pancreatic cancer growth through a Kras-regulated metabolic pathway

TLDR
The identification of a non-canonical pathway of glutamine use in human pancreatic ductal adenocarcinoma (PDAC) cells is reported and it is established that the reprogramming of glutamines metabolism is mediated by oncogenic KRAS, the signature genetic alteration in PDAC, through the transcriptional upregulation and repression of key metabolic enzymes in this pathway.

The SIRT1/HIF2α axis drives reductive glutamine metabolism under chronic acidosis and alters tumor response to therapy.

TLDR
It is demonstrated that long-term exposure of cancer cells to acidic pH leads to a metabolic reprogramming toward glutamine metabolism, triggered by the need to reduce the production of protons from glycolysis and further maintained by the NAD(+)-dependent increase in SIRT1 deacetylase activity to ensure intracellular pH homeostasis.

PGC-1α supports glutamine metabolism in breast cancer

TLDR
It is shown that PGC-1α expression is positively correlated with that of the glutamine pathway in ERBB2+ breast cancer patients, and high expression of this pathway is associated with reduced patient survival, suggesting that targeting glutamine metabolism may have therapeutic potential in the treatment of ER BB2- breast cancer.

Reductive carboxylation supports growth in tumor cells with defective mitochondria

TLDR
These findings reveal the novel induction of a versatile glutamine-dependent pathway that reverses many of the reactions of the canonical CAC, supports tumour cell growth, and explains how cells generate pools of CAC intermediates in the face of impaired mitochondrial metabolism.

Reductive glutamine metabolism is a function of the α-ketoglutarate to citrate ratio in cells.

TLDR
It is demonstrated that reductive glutamine metabolism is initiated in response to perturbations that result in an increase in the α-ketoglutarate/citrate ratio, which might require distinct modulations of metabolite concentrations rather than targeting the upstream signalling.