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Glutamine Addiction In Gliomas

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Abstract

Cancer cells develop and succeed by shifting to different metabolic programs compared with their normal cell counterparts. One of the classical hallmarks of cancer cells is their higher glycolysis rate and lactate production even in the presence of abundant O2 (Warburg effect). Another common metabolic feature of cancer cells is a high rate of glutamine (Gln) consumption normally exceeding their biosynthetic and energetic needs. The term Gln addiction is now widely used to reflect the strong dependence shown by most cancer cells for this essential nitrogen substrate after metabolic reprogramming. A Gln/glutamate (Glu) cycle occurs between host tissues and the tumor in order to maximize its growth and proliferation rates. The mechanistic basis for this deregulated tumor metabolism and how these changes are connected to oncogenic and tumor suppressor pathways are becoming increasingly understood. Based on these advances, new avenues of research have been initiated to find novel therapeutic targets and to explore strategies that interfere with glutamine metabolism as anticancer therapies. In this review, we provided an updated overview of glutamine addiction in glioma, the most prevalent type of brain tumor.

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Fig. 1

Adapted from Brennan et al., 2013 [19]. (Color figure online)

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Abbreviations

α-KG:

2-oxoglutarate

AMPARs:

α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors

BPTES:

[bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl)ethyl sulfide]

NEAA:

Non-essential amino acids

DON:

6-diazo-5-oxo-l-norleucine

EATC:

Ehrlich ascites tumor cells

GBM:

Glioblastoma multiforme

GDH:

Glutamate dehydrogenase

GS:

Glutamine synthetase

GSH:

Reduced glutathione

HDAC:

Histone deacetylase

IDH1:

Isocitrate dehydrogenase 1

mTORC1:

Mammalian target of rapamycin complex 1

NF-κB:

Nuclear factor-kappa B

NMDARs:

N-methyl-d-aspartate receptors

OXPHOS:

Oxidative phosphorylation

ROS:

Reactive oxygen species

T-ALL:

T-cell acute lymphoblastic leukemia

TCA:

Tricarboxylic acid cycle

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Acknowledgements

The work performed by the Canceromics group and cited in this article was financially supported by Grant SAF2015-64501-R from the Spanish Ministry of Economy and Competitivity (to JM and JMM) and Grant RD12/0028/0013 (JM) of the RTA RETICS network from the Spanish Health Institute Carlos III.

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Authors and Affiliations

  1. Canceromics lab, Departamento de Biología Molecular y Bioquímica, Facultad de Ciencias, Instituto de Biomedicina de Málaga (IBIMA), Universidad de Málaga, 29071, Málaga, Spain

    Javier Márquez, Francisco J. Alonso, José M. Matés, Juan A. Segura, Mercedes Martín-Rufián & José A. Campos-Sandoval

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  1. Javier Márquez
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  2. Francisco J. Alonso
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  3. José M. Matés
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Correspondence to Javier Márquez.

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Márquez, J., Alonso, F.J., Matés, J.M. et al. Glutamine Addiction In Gliomas. Neurochem Res 42, 1735–1746 (2017). https://doi.org/10.1007/s11064-017-2212-1

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