Fig. 7

ARPC1B expression is reflective of sensitivity to the ATR inhibitor AZD6738. A Heatmap visualizing the difference in sensitivity of cell lines with high and low expression of ARPC1B to the indicated drugs. B Western blot analysis of ATR, IFI16 and HuR protein expression upon AZD6738 treatment in GSCs. β-Actin served as the control. C Quantification of apoptosis rates of GSC 267 and GSC 20 cells with the indicated treatments. D The DNA damage assessed by the comet assay was quantified for GSC 267 and GSC 20 cells treated with the indicated interventions. E Bioluminescence imaging of tumor size on day 30 in GSC 267 xenograft nude mice treated with the indicated interventions. F The quantification of photon counts on day 30 of the GSC 267 xenografts. G Kaplan–Meier curves visualizing the survival of GSC 267 xenograft mice in different treatment groups. H The graphical model of this study. ARPC1B was upregulated in MES-GSCs and overexpression of ARPC1B in PN-GSCs facilitated the transition to MES-GSCs. ARPC1B suppressed TRIM21-mediated degradation of IFI16 and HuR, thereby activating NF-κB and STAT3, which promoted PMT and counteracted the tumoricidal effect of IR. AZD6738, as a selective ATR inhibitor, exhibited promising anti-GSCs effect in combination with IR