Lactate dehydrogenases promote glioblastoma growth and invasion via a metabolic symbiosis
Abstract: Lactate is a central metabolite in brain physiology but also contributes to tumor development. Glioblastoma (GB) is the most common and malignant primary brain tumor in adults, recognized by angiogenic and invasive growth, in addition to its altered metabolism. We show herein that lactate fuels GB anaplerosis by replenishing the tricarboxylic acid (TCA) cycle in absence of glucose. Lactate dehydrogenases (LDHA and LDHB), which we found spatially expressed in GB tissues, catalyze the interconversion of pyruvate and lactate. However, ablation of both LDH isoforms, but not only one, led to a reduction in tumor growth and an increase in mouse survival. Comparative transcriptomics and metabolomics revealed metabolic rewiring involving high oxidative phosphorylation (OXPHOS) in the LDHA/B KO group which sensitized tumors to cranial irradiation, thus improving mouse survival. When mice were treated with the antiepileptic drug stiripentol, which targets LDH activity, tumor growth decreased. Our findings unveil the complex metabolic network in which both LDHA and LDHB are integrated and show that the combined inhibition of LDHA and LDHB strongly sensitizes GB to therapy.
- Standort
-
Deutsche Nationalbibliothek Frankfurt am Main
- Umfang
-
Online-Ressource
- Sprache
-
Englisch
- Erschienen in
-
Lactate dehydrogenases promote glioblastoma growth and invasion via a metabolic symbiosis ; day:24 ; month:10 ; year:2022 ; extent:20
EMBO molecular medicine / European Molecular Biology Organization ; (24.10.2022) (gesamt 20)
- Urheber
-
Guyon, Joris
Fernandez‐Moncada, Ignacio
Larrieu, Claire M.
Bouchez, Cyrielle L.
Pagano Zottola, Antonio C.
Galvis, Johanna
Chouleur, Tiffanie
Burban, Audrey
Joseph, Kevin
Ravi, Vidhya M.
Espedal, Heidi
Røsland, Gro Vatne
Daher, Boutaina
Barre, Aurélien
Dartigues, Benjamin
Karkar, Slim
Rudewicz, Justine
Romero‐Garmendia, Irati
Klink, Barbara
Grützmann, Konrad
Derieppe, Marie‐Alix
Molinié, Thibaut
Obad, Nina
Léon, Céline
Seano, Giorgio
Miletic, Hrvoje
Heiland, Dieter Henrik
Marsicano, Giovanni
Nikolski, Macha
Bjerkvig, Rolf
Bikfalvi, Andreas
Daubon, Thomas
- DOI
-
10.15252/emmm.202115343
- URN
-
urn:nbn:de:101:1-2022102415021797005862
- Rechteinformation
-
Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Letzte Aktualisierung
-
15.08.2025, 07:26 MESZ
Datenpartner
Deutsche Nationalbibliothek. Bei Fragen zum Objekt wenden Sie sich bitte an den Datenpartner.
Beteiligte
- Guyon, Joris
- Fernandez‐Moncada, Ignacio
- Larrieu, Claire M.
- Bouchez, Cyrielle L.
- Pagano Zottola, Antonio C.
- Galvis, Johanna
- Chouleur, Tiffanie
- Burban, Audrey
- Joseph, Kevin
- Ravi, Vidhya M.
- Espedal, Heidi
- Røsland, Gro Vatne
- Daher, Boutaina
- Barre, Aurélien
- Dartigues, Benjamin
- Karkar, Slim
- Rudewicz, Justine
- Romero‐Garmendia, Irati
- Klink, Barbara
- Grützmann, Konrad
- Derieppe, Marie‐Alix
- Molinié, Thibaut
- Obad, Nina
- Léon, Céline
- Seano, Giorgio
- Miletic, Hrvoje
- Heiland, Dieter Henrik
- Marsicano, Giovanni
- Nikolski, Macha
- Bjerkvig, Rolf
- Bikfalvi, Andreas
- Daubon, Thomas
Ähnliche Objekte (12)
Lactate dehydrogenases promote glioblastoma growth and invasion via a metabolic symbiosis
Lactate dehydrogenase A regulates tumor-macrophage symbiosis to promote glioblastoma progression
D- and L-lactate dehydrogenases during invertebrate evolution
Lactate oxidative phosphorylation by annulus fibrosus cells: evidence for lactate-dependent metabolic symbiosis in intervertebral discs
Genetic diversity of Plasmodium vivax and Plasmodium falciparum lactate dehydrogenases in Myanmar isolates
Diverse allosteric and catalytic functions of tetrameric d-lactate dehydrogenases from three Gram-negative bacteria
(R/S)-lactate/2-hydroxybutyrate dehydrogenases in and biosynthesis of block copolyesters by Ralstonia eutropha
Symbiosis
Production of l-lactic acid by the yeast Candida sonorensis expressing heterologous bacterial and fungal lactate dehydrogenases
Perioperative cerebral ischemia promote infiltrative recurrence in glioblastoma
Superstratum symbiosis
Inhibition of short-chain dehydrogenases
Lactate dehydrogenases promote glioblastoma growth and invasion via a metabolic symbiosis
Lactate dehydrogenase A regulates tumor-macrophage symbiosis to promote glioblastoma progression
D- and L-lactate dehydrogenases during invertebrate evolution
Lactate oxidative phosphorylation by annulus fibrosus cells: evidence for lactate-dependent metabolic symbiosis in intervertebral discs
Genetic diversity of Plasmodium vivax and Plasmodium falciparum lactate dehydrogenases in Myanmar isolates
Diverse allosteric and catalytic functions of tetrameric d-lactate dehydrogenases from three Gram-negative bacteria
(R/S)-lactate/2-hydroxybutyrate dehydrogenases in and biosynthesis of block copolyesters by Ralstonia eutropha
Symbiosis
Production of l-lactic acid by the yeast Candida sonorensis expressing heterologous bacterial and fungal lactate dehydrogenases
Perioperative cerebral ischemia promote infiltrative recurrence in glioblastoma
Superstratum symbiosis
Inhibition of short-chain dehydrogenases
Lactate dehydrogenases promote glioblastoma growth and invasion via a metabolic symbiosis
Lactate dehydrogenase A regulates tumor-macrophage symbiosis to promote glioblastoma progression
D- and L-lactate dehydrogenases during invertebrate evolution
Lactate oxidative phosphorylation by annulus fibrosus cells: evidence for lactate-dependent metabolic symbiosis in intervertebral discs
Genetic diversity of Plasmodium vivax and Plasmodium falciparum lactate dehydrogenases in Myanmar isolates
Diverse allosteric and catalytic functions of tetrameric d-lactate dehydrogenases from three Gram-negative bacteria
(R/S)-lactate/2-hydroxybutyrate dehydrogenases in and biosynthesis of block copolyesters by Ralstonia eutropha
Symbiosis
Production of l-lactic acid by the yeast Candida sonorensis expressing heterologous bacterial and fungal lactate dehydrogenases
Perioperative cerebral ischemia promote infiltrative recurrence in glioblastoma
Superstratum symbiosis