CSIG-17. SCD5 PROTECTS GLIOBLASTOMA STEM CELLS FROM DEATH AND DIFFERENTIATION BY MODULATING INTRACELLULAR LIPID COMPOSITION

Abstract Glioblastoma (GBM) is the most common malignant brain cancer in adults, enriched a small subpopulation of glioma stem cells (GSC), which can drive tumor recurrence and therapeutic resistance. Considerable evidence suggests that endogenous levels unsaturated fatty acids (FA) are crucial regulators GSCs survival self-renewal. Stearoyl-CoA desaturase-1 (SCD-1) abundant desaturase humans. We have previously shown SCD1 activity required for self-renewal initiation. However, orthologous isoform, SCD5, has been poorly characterized its potential role GBM not reported. observed SCD5 highly GSC both at mRNA protein levels. Genetic downregulation led to remarkable decrease cell markers, impaired viability ability form neurospheres. Further, orthotopically implanted mice resulted delayed growth extended overall survival. Shotgun lipidomics after either or knock-down revealed largely distinctive lipidome profile, highlighting divergent these two isoforms lipid metabolism. Surprisingly, analysis showed synthesize variety species involved receptor tyrosine kinase (RTKs) GPCRs signal transduction, directly linking FA synthesis with oncogenic signaling. confirmed results by immunoblot analysis. Using specific tagging immunofluorescence analysis, we that, despite spatial overlap expression, uniquely present some subcellular locations. This different functions could be related localization. Altogether, our underscore novel function SCD metabolism highlight as target GBM.