The impact of inhibiting the Hippo signaling pathway effector molecule YAP1 on in vitro glioblastoma and glioblastoma stem cells

Glioblastoma, a prevalent and aggressive brain tumor in adults, recurs due to local invasiveness, radiation therapy failure, drug resistance, and cancer stem cell presence. The Hippo signaling pathway, regulating organ size and growth, features YAP as a key effector with oncogenic implications in various cancers, including glioma. This study aimed to explore YAP1 as a therapeutic target in glioblastoma by silencing it using siRNA and evaluating the potential of a new inhibitor, CA3 (CIL56), through advanced in vitro analyses. Investigations were conducted on brain cancer and stem cells, alongside healthy brain stem cells and human brain microvascular endothelial cells. Effects of CA3 (CIL56) and YAP1 siRNA on cell lines were gauged through Annexin V-FITC assay, ferroptosis assay (GPX activity), and cell cycle analysis. Invasion and migration assays, along with epithelial-mesenchymal transition marker evaluations, assessed cell movement effects. Spheroid formation examined stemness effects, with qRT-PCR measuring gene expression changes. Findings indicate that siRNA-mediated YAP1 silencing and CA3 (CIL56) inhibition exert significant, though varying, anti-tumoral effects on glioblastoma cell viability, motility, and stemness. Notably, CA3's impact on stem cells highlights its potential as a promising therapeutic target, meriting further investigation.