Negative allosteric modulators of metabotropic glutamate receptor 3 target the stem-like phenotype of glioblastoma.

ABSTRACT: Glioblastoma is an invariably deadly disease. A subpopulation of glioma stem-like cells (GSCs) drives tumor progression and treatment resistance. Two recent studies demonstrated that neurons form oncogenic glutamatergic electrochemical synapses with post-synaptic GSCs. This led us to explore whether glutamate signaling through G protein-coupled metabotropic receptors would also contribute to the malignancy of glioblastoma. We found that glutamate metabotropic receptor (Grm)3 is the predominantly expressed Grm in glioblastoma. Associations of GRM3 gene expression levels with survival are confined to the proneural gene expression subtype, which is associated with enrichment of GSCs. Using multiplexed single-cell qRT-PCR, GSC marker-based cell sorting, database interrogations, and func

SUBMITTER: Wirsching HG 

PROVIDER: S-EPMC7851500 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature