GABA_A receptor agonist suppresses pediatric medulloblastoma progression by inhibiting PKA-Gli1 signaling axis.

ABSTRACT: The Sonic hedgehog-activated subgroup of medulloblastoma (SHH-MB) is one of the most common malignant pediatric brain tumors. Recent clinical studies and genomic databases indicate that GABA_A receptor holds significant clinical relevance as a therapeutic target for pediatric MB. Herein, we report that "moxidectin," a GABA_A receptor agonist, inhibits the proliferation of Daoy, UW426, UW228, ONS76, and PFSK1 SHH-MB cells by inducing apoptosis. Immunoblotting and immunofluorescence microscopy demonstrated that moxidectin significantly induced GABA_A receptor expression and inhibited cyclic AMP (cAMP)-mediated protein kinase A (PKA)-cAMP response element-binding protein (CREB)-Gli1 signaling in SHH-MB. Gli1 and the downstream effector cancer stem cell (CSC) mole

SUBMITTER: Kaushik I 

PROVIDER: S-EPMC9263240 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature