Hypoxia and oxygenation induce a metabolic switch between pentose phosphate pathway and glycolysis in glioma stem-like cells

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Hypoxia and oxygenation induce a metabolic switch between pentose phosphate pathway and glycolysis in glioma stem-like cells. / Kathagen, Annegret; Schulte, Alexander; Balcke, Gerd; Phillips, Heidi S; Martens, Tobias; Matschke, Jakob; Günther, Hauke S; Soriano, Robert; Modrusan, Zora; Sandmann, Thomas; Kuhl, Carsten; Tissier, Alain; Holz, Mareike; Krawinkel, Lutz A; Glatzel, Markus; Westphal, Manfred; Lamszus, Katrin.

in: ACTA NEUROPATHOL, Jahrgang 126, Nr. 5, 01.11.2013, S. 763-80.

Publikationen: SCORING: Beitrag in Fachzeitschrift/ZeitungSCORING: ZeitschriftenaufsatzForschungBegutachtung

Harvard

Kathagen, A, Schulte, A, Balcke, G, Phillips, HS, Martens, T, Matschke, J, Günther, HS, Soriano, R, Modrusan, Z, Sandmann, T, Kuhl, C, Tissier, A, Holz, M, Krawinkel, LA, Glatzel, M, Westphal, M & Lamszus, K 2013, 'Hypoxia and oxygenation induce a metabolic switch between pentose phosphate pathway and glycolysis in glioma stem-like cells', ACTA NEUROPATHOL, Jg. 126, Nr. 5, S. 763-80. https://doi.org/10.1007/s00401-013-1173-y

APA

Kathagen, A., Schulte, A., Balcke, G., Phillips, H. S., Martens, T., Matschke, J., Günther, H. S., Soriano, R., Modrusan, Z., Sandmann, T., Kuhl, C., Tissier, A., Holz, M., Krawinkel, L. A., Glatzel, M., Westphal, M., & Lamszus, K. (2013). Hypoxia and oxygenation induce a metabolic switch between pentose phosphate pathway and glycolysis in glioma stem-like cells. ACTA NEUROPATHOL, 126(5), 763-80. https://doi.org/10.1007/s00401-013-1173-y

Vancouver

Bibtex

@article{8a54a6f6a4584d84a5994eff8b4678e2,
title = "Hypoxia and oxygenation induce a metabolic switch between pentose phosphate pathway and glycolysis in glioma stem-like cells",
abstract = "Fluctuations in oxygen tension during tissue remodeling impose a major metabolic challenge in human tumors. Stem-like tumor cells in glioblastoma, the most common malignant brain tumor, possess extraordinary metabolic flexibility, enabling them to initiate growth even under non-permissive conditions. We identified a reciprocal metabolic switch between the pentose phosphate pathway (PPP) and glycolysis in glioblastoma stem-like (GS) cells. Expression of PPP enzymes is upregulated by acute oxygenation but downregulated by hypoxia, whereas glycolysis enzymes, particularly those of the preparatory phase, are regulated inversely. Glucose flux through the PPP is reduced under hypoxia in favor of flux through glycolysis. PPP enzyme expression is elevated in human glioblastomas compared to normal brain, especially in highly proliferative tumor regions, whereas expression of parallel preparatory phase glycolysis enzymes is reduced in glioblastomas, except for strong upregulation in severely hypoxic regions. Hypoxia stimulates GS cell migration but reduces proliferation, whereas oxygenation has opposite effects, linking the metabolic switch to the {"}go or grow{"} potential of the cells. Our findings extend Warburg's observation that tumor cells predominantly utilize glycolysis for energy production, by suggesting that PPP activity is elevated in rapidly proliferating tumor cells but suppressed by acute severe hypoxic stress, favoring glycolysis and migration to protect cells against hypoxic cell damage.",
keywords = "Animals, Apoptosis, Cell Hypoxia, Cell Proliferation, Cells, Cultured, Flow Cytometry, Glioma, Glycolysis, Heterografts, Humans, Immunohistochemistry, Mice, Mice, Nude, Neoplastic Stem Cells, Oxygen, Pentose Phosphate Pathway, Real-Time Polymerase Chain Reaction, Transcriptome",
author = "Annegret Kathagen and Alexander Schulte and Gerd Balcke and Phillips, {Heidi S} and Tobias Martens and Jakob Matschke and G{\"u}nther, {Hauke S} and Robert Soriano and Zora Modrusan and Thomas Sandmann and Carsten Kuhl and Alain Tissier and Mareike Holz and Krawinkel, {Lutz A} and Markus Glatzel and Manfred Westphal and Katrin Lamszus",
year = "2013",
month = nov,
day = "1",
doi = "10.1007/s00401-013-1173-y",
language = "English",
volume = "126",
pages = "763--80",
journal = "ACTA NEUROPATHOL",
issn = "0001-6322",
publisher = "Springer",
number = "5",

}

RIS

TY - JOUR

T1 - Hypoxia and oxygenation induce a metabolic switch between pentose phosphate pathway and glycolysis in glioma stem-like cells

AU - Kathagen, Annegret

AU - Schulte, Alexander

AU - Balcke, Gerd

AU - Phillips, Heidi S

AU - Martens, Tobias

AU - Matschke, Jakob

AU - Günther, Hauke S

AU - Soriano, Robert

AU - Modrusan, Zora

AU - Sandmann, Thomas

AU - Kuhl, Carsten

AU - Tissier, Alain

AU - Holz, Mareike

AU - Krawinkel, Lutz A

AU - Glatzel, Markus

AU - Westphal, Manfred

AU - Lamszus, Katrin

PY - 2013/11/1

Y1 - 2013/11/1

N2 - Fluctuations in oxygen tension during tissue remodeling impose a major metabolic challenge in human tumors. Stem-like tumor cells in glioblastoma, the most common malignant brain tumor, possess extraordinary metabolic flexibility, enabling them to initiate growth even under non-permissive conditions. We identified a reciprocal metabolic switch between the pentose phosphate pathway (PPP) and glycolysis in glioblastoma stem-like (GS) cells. Expression of PPP enzymes is upregulated by acute oxygenation but downregulated by hypoxia, whereas glycolysis enzymes, particularly those of the preparatory phase, are regulated inversely. Glucose flux through the PPP is reduced under hypoxia in favor of flux through glycolysis. PPP enzyme expression is elevated in human glioblastomas compared to normal brain, especially in highly proliferative tumor regions, whereas expression of parallel preparatory phase glycolysis enzymes is reduced in glioblastomas, except for strong upregulation in severely hypoxic regions. Hypoxia stimulates GS cell migration but reduces proliferation, whereas oxygenation has opposite effects, linking the metabolic switch to the "go or grow" potential of the cells. Our findings extend Warburg's observation that tumor cells predominantly utilize glycolysis for energy production, by suggesting that PPP activity is elevated in rapidly proliferating tumor cells but suppressed by acute severe hypoxic stress, favoring glycolysis and migration to protect cells against hypoxic cell damage.

AB - Fluctuations in oxygen tension during tissue remodeling impose a major metabolic challenge in human tumors. Stem-like tumor cells in glioblastoma, the most common malignant brain tumor, possess extraordinary metabolic flexibility, enabling them to initiate growth even under non-permissive conditions. We identified a reciprocal metabolic switch between the pentose phosphate pathway (PPP) and glycolysis in glioblastoma stem-like (GS) cells. Expression of PPP enzymes is upregulated by acute oxygenation but downregulated by hypoxia, whereas glycolysis enzymes, particularly those of the preparatory phase, are regulated inversely. Glucose flux through the PPP is reduced under hypoxia in favor of flux through glycolysis. PPP enzyme expression is elevated in human glioblastomas compared to normal brain, especially in highly proliferative tumor regions, whereas expression of parallel preparatory phase glycolysis enzymes is reduced in glioblastomas, except for strong upregulation in severely hypoxic regions. Hypoxia stimulates GS cell migration but reduces proliferation, whereas oxygenation has opposite effects, linking the metabolic switch to the "go or grow" potential of the cells. Our findings extend Warburg's observation that tumor cells predominantly utilize glycolysis for energy production, by suggesting that PPP activity is elevated in rapidly proliferating tumor cells but suppressed by acute severe hypoxic stress, favoring glycolysis and migration to protect cells against hypoxic cell damage.

KW - Animals

KW - Apoptosis

KW - Cell Hypoxia

KW - Cell Proliferation

KW - Cells, Cultured

KW - Flow Cytometry

KW - Glioma

KW - Glycolysis

KW - Heterografts

KW - Humans

KW - Immunohistochemistry

KW - Mice

KW - Mice, Nude

KW - Neoplastic Stem Cells

KW - Oxygen

KW - Pentose Phosphate Pathway

KW - Real-Time Polymerase Chain Reaction

KW - Transcriptome

U2 - 10.1007/s00401-013-1173-y

DO - 10.1007/s00401-013-1173-y

M3 - SCORING: Journal article

C2 - 24005892

VL - 126

SP - 763

EP - 780

JO - ACTA NEUROPATHOL

JF - ACTA NEUROPATHOL

SN - 0001-6322

IS - 5

ER -