TY - JOUR

T1 - Replication Protein A (RPA) Mediates Radio-Resistance of Glioblastoma Cancer Stem-Like Cells

AU - Pedersen, Henriette

AU - Obara, Elisabeth Anne Adanma

AU - Elbæk, Kirstine Juul

AU - Vitting-Serup, Kristoffer

AU - Hamerlik, Petra

PY - 2020

Y1 - 2020

N2 - Glioblastoma (GBM) is among the deadliest of solid tumors with median survival rates of approximately 12–15 months despite maximal therapeutic intervention. A rare population of self-renewing cells referred to as GBM cancer stem-like cells (GSCs) are believed to be the source of inevitable recurrence in GBM. GSCs exhibit preferential activation of the DNA damage response pathway (DDR) and evade ionizing radiation (IR) therapy by superior execution of DNA repair compared to their differentiated counterparts, differentiated GBM cells (DGCs). Replication Protein A (RPA) plays a central role in most of the DNA metabolic processes essential for genomic stability, including DNA repair. Here, we show that RPA is preferentially expressed by GSCs and high RPA expression informs poor glioma patient survival. RPA loss either by shRNA-mediated silencing or chemical inhibition impairs GSCs’ survival and self-renewal and most importantly, sensitizes these cells to IR. This newly uncovered role of RPA in GSCs supports its potential clinical significance as a druggable biomarker in GBM.

AB - Glioblastoma (GBM) is among the deadliest of solid tumors with median survival rates of approximately 12–15 months despite maximal therapeutic intervention. A rare population of self-renewing cells referred to as GBM cancer stem-like cells (GSCs) are believed to be the source of inevitable recurrence in GBM. GSCs exhibit preferential activation of the DNA damage response pathway (DDR) and evade ionizing radiation (IR) therapy by superior execution of DNA repair compared to their differentiated counterparts, differentiated GBM cells (DGCs). Replication Protein A (RPA) plays a central role in most of the DNA metabolic processes essential for genomic stability, including DNA repair. Here, we show that RPA is preferentially expressed by GSCs and high RPA expression informs poor glioma patient survival. RPA loss either by shRNA-mediated silencing or chemical inhibition impairs GSCs’ survival and self-renewal and most importantly, sensitizes these cells to IR. This newly uncovered role of RPA in GSCs supports its potential clinical significance as a druggable biomarker in GBM.

KW - Cancer stem-like cells

KW - DNA damage

KW - Glioblastoma

KW - Radio-resistance

KW - RPA

U2 - 10.3390/ijms21051588

DO - 10.3390/ijms21051588

M3 - Journal article

C2 - 32111042

AN - SCOPUS:85079842613

VL - 21

JO - International Journal of Molecular Sciences (Online)

JF - International Journal of Molecular Sciences (Online)

SN - 1661-6596

IS - 5

M1 - 1588

ER -