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/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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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 -