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Methodological Approaches for Assessing Metabolomic Changes in Glioblastomas

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Autophagy and Cancer

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2445))

Abstract

Glioblastoma (GBM), a highly malignant primary brain tumor, inevitably leads to death. In the last decade, a variety of novel molecular characteristics of GBMs were unraveled. The identification of the mutation in the IDH1 and less commonly IDH2 gene was surprising and ever since has nurtured research in the field of GBM metabolism. While initially thought that mutated IDH1 were to act as a loss of function mutation it became clear that it conferred the production of an oncometabolite that in turn substantially reprograms GBM metabolism. While mutated IDH1 represents truly the tip of the iceberg, there are numerous other related observations in GBM that are of significant interest to the field, including the notion that oxidative metabolism appears to play a more critical role than believed earlier. Metabolic zoning is another important hallmark of GBM since it was found that the infiltrative margin that drives GBM progression reveals enrichment of fatty acid derivatives. Consistently, fatty acid metabolism appears to be a novel therapeutic target for GBM. How metabolism in GBM intersects is another pivotal issue that appears to be important for its progression and response and resistance to therapies. In this review, we will summarize some of the most relevant findings related to GBM metabolism and cell death and how these observations are influencing the field. We will provide current approaches that are applied in the field to measure metabolomic changes in GBM models, including the detection of unlabeled and labeled metabolites as well as extracellular flux analysis.

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Abbreviations

2-HG:

2-Hydroxyglutarate

3-PGA:

3-Phosphoglyceric acid

Acetyl-CoA:

Acetyl coenzyme A

ATF3:

Activating transcription factor 3

ATF4:

Activating transcription factor 4

ATP:

Adenosine triphosphate

BAK:

Bcl-2 homologous antagonist killer

Bcl-xL:

Bcl-2-like protein 1

BODIPY C11:

Lipid peroxidation sensor

c-FLIP:

FLICE-like inhibitory protein

CPT1A:

Carnitine palmitoyltransferase 1A

crm-A:

Caspase-8 inhibitor

CRISPR/Cas9:

CRISPR-associated Protein 9

EGFR:

Epidermal growth factor receptor

FAD:

Flavin adenine dinucleotide

FADH:

Is the reduced form of flavin adenine dinucleotide (FAD)

FDA:

Food and Drug Administration

GPX4:

Glutathione peroxidase 4

IDH1 :

Isocitrate dehydrogenases 1

IDH2:

Isocitrate dehydrogenases 2

IDH3:

Isocitrate dehydrogenases 3

IKKB:

Inhibitor of nuclear factor kappa B kinase subunit beta

KRAS:

KRAS proto-oncogene, GTPase

MAPK:

Mitogen-activated protein kinase

Mcl-1:

MCL1 apoptosis regulator, BCL2 family member

MET:

MET proto-oncogene, receptor tyrosine kinase

mTORC1 :

Mammalian target of rapamycin complex 1

mTORC2:

Mammalian target of rapamycin complex 2

NAD:

Nicotinamide adenine dinucleotide

NADH:

The reduced form of nicotinamide adenine dinucleotide

NADPH2:

Nicotinamide adenine dinucleotide phosphate

PEA15:

Proliferation and apoptosis adaptor protein 15

PHGDH:

Phosphoglycerate dehydrogenase

PSAT1:

Phosphoserine aminotransferase 1

PSPH:

Phosphoserine phosphatase

SHMT:

Serine hydroxymethyltransferase

SLC1A5:

Solute carrier family 1 member 5

SLC7A11:

Cystine/glutamate antiporter xCT

SMARCA4:

Transcription activator BRG1 (Brahma-related gene-1)

TCA cycle:

Tricarboxylic acid cycle

Usp9X:

Ubiquitin specific peptidase 9 X-linked

XIAP:

X-Linked inhibitor of apoptosis

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Authors and Affiliations

  1. Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY, USA

    Trang T. T. Nguyen & Markus D. Siegelin

  2. Department of Biological Sciences, Bronx Community College, City University of New York, Bronx, NY, USA

    Enyuan Shang

  3. Department of Pediatrics and Adolescent Medicine, Ulm University Medical Center, Ulm, Germany

    Mike-Andrew Westhoff

  4. Department of Neurosurgery, Ulm University Medical Center, Ulm, Germany

    Georg Karpel-Massler

Authors
  1. Trang T. T. Nguyen
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  2. Enyuan Shang
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  3. Mike-Andrew Westhoff
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  4. Georg Karpel-Massler
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  5. Markus D. Siegelin
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Corresponding author

Correspondence to Markus D. Siegelin .

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Editors and Affiliations

  1. Karolinska Institute, Stockholm, Sweden

    Helin Norberg

  2. Karolinska Institute, Stockholm, Sweden

    Erik Norberg

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The authors declare no competing interests.

Funding

M.D. Siegelin: NIH NINDS R01 NS095848, R01NS102366, R01NS113793, K08NS083732, Louis V. Gerstner, Jr. Scholars Program (2017–2020) and Schaefer Research Scholars Program Awards 2020. Trang T.T. Nguyen: American Brain Tumor Association Basic Research Fellowship in Memory of Katie Monson (BRF1900018).

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Nguyen, T.T.T., Shang, E., Westhoff, MA., Karpel-Massler, G., Siegelin, M.D. (2022). Methodological Approaches for Assessing Metabolomic Changes in Glioblastomas. In: Norberg, H., Norberg, E. (eds) Autophagy and Cancer. Methods in Molecular Biology, vol 2445. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-2071-7_19

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  • DOI: https://doi.org/10.1007/978-1-0716-2071-7_19

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  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-2070-0

  • Online ISBN: 978-1-0716-2071-7

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