Spt6 REGULATES TRANSCRIPTION BY STABILIZING RNA Pol II AND SO DRIVES GLIOBLASTOMA CANCER STEM-LIKE CELL MAINTENANCE

Glioblastoma (GBM) is the most advanced and lethal tumor with epigenetically distinct cancer stem-like cells (CSCs) resistant to chemo- and radio-therapy. Spt6 is a histone chaperon involved in nucleosome assembly and regulates RNA polymerase II-mediated transcription. Our preliminary data identified Spt6 to be crucial for glioblastoma stem cells (GSCs) genomic stability and survival. Spt6 depletion in GSCs decreased global transcription rates and cell cycle entry. Cycloheximide and proteasome inhibitor (MG132) experiments confirmed that Spt6 stabilizes RNA polymerase II and so regulates GSC maintenance at a transcriptional level. Spt6 loss impaired GSC survival in vitro and tumor initiating capacity in vivo, thereby making it an attractive target for glioblastoma therapy.