• FDFT1 is upregulated in glioblastoma stem cells (GSCs) compared to differentiated cells, highlighting its role in maintaining stemness.
• Knockdown of FDFT1 suppresses GBM cell proliferation and migration and enhances sensitivity to temozolomide, suggesting a therapeutic target.
• FDFT1 is transcriptionally regulated by SREBP2 and activates the AKT pathway, linking mevalonate metabolism to tumor progression.
• Inhibition of FDFT1 with YM-53601 or simvastatin induces apoptosis in GSCs, offering a potential strategy to eliminate these therapy-resistant cells.