Replication Stress Drives Constitutive Activation of the DNA Damage Response and Radioresistance in Glioblastoma Stem-like Cells.

ABSTRACT: Glioblastoma (GBM) is a lethal primary brain tumor characterized by treatment resistance and inevitable tumor recurrence, both of which are driven by a subpopulation of GBM cancer stem-like cells (GSC) with tumorigenic and self-renewal properties. Despite having broad implications for understanding GSC phenotype, the determinants of upregulated DNA-damage response (DDR) and subsequent radiation resistance in GSC are unknown and represent a significant barrier to developing effective GBM treatments. In this study, we show that constitutive DDR activation and radiation resistance are driven by high levels of DNA replication stress (RS). CD133⁺ GSC exhibited reduced DNA replication velocity and a higher frequency of stalled replication forks than CD133^- non-GSC in vit

SUBMITTER: Carruthers RD 

PROVIDER: S-EPMC6128404 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature