articleNature CommunicationsMar 5, 2024GOLD OA

Lactate dehydrogenase A regulates tumor-macrophage symbiosis to promote glioblastoma progression

FKFatima KhanYLYiyun LinHAHeba AliLPLizhi PangMDMadeline Dunterman

Northwestern University · Neurological Surgery · +6 more institutions

PubMed
Indexed incrossrefdoajpubmed

Abstract

Abundant macrophage infiltration and altered tumor metabolism are two key hallmarks of glioblastoma. By screening a cluster of metabolic small-molecule compounds, we show that inhibiting glioblastoma cell glycolysis impairs macrophage migration and lactate dehydrogenase inhibitor stiripentol emerges as the top hit. Combined profiling and functional studies demonstrate that lactate dehydrogenase A (LDHA)-directed extracellular signal-regulated kinase (ERK) pathway activates yes-associated protein 1 (YAP1)/ signal transducer and activator of transcription 3 (STAT3) transcriptional co-activators in glioblastoma cells to upregulate C-C motif chemokine ligand 2 (CCL2) and CCL7, which recruit macrophages into the…

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122
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Authors

15

Topics & keywords

Topics
Keywords
  • Lactate dehydrogenase A
  • Cancer research
  • Tumor microenvironment
  • Biology
  • CCL3
  • Cell biology
  • STAT3
  • STAT protein
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