Fig. 3.

Cyclin-dependent kinase 18 (CDK18) regulates MYC/MYCN-induced poly(ADP-ribose) polymerase inhibitor sensitivity in glioblastoma stem-like cells. a, b Effect of CDK18 expression on olaparib sensitivity. (left) Western blots showing CDK18 overexpression or knockdown with (+) or without (−) doxycycline (Dox). (right) Olaparib dose–response curves. a MGG4-control (Con)/MGG4-CDK18 (upper) and MGG8-control (Con)/MGG8-CDK18 (lower). b BT74-shControl (shCon)/BT74-shCDK18 (upper) and MGG18-shControl (shCon)/MGG18-shCDK18 (lower) (shCDK18; two independent sequences), with (+) or without (−) Dox. c Treatment schedule for d, e. Details as in Fig. 1g. d, e Kaplan–Meier survival curves of mice bearing orthotopic MGG4-CDK18 (d) or BT74-shCDK18#2 (e) xenografts treated with olaparib (Ola) or vehicle (Veh) with (+) or without (−) Dox. MST median survival time. Vertical lines indicate p value comparisons (log-rank test). f, g Olaparib dose responses in MGG4 with knockdown of MYC alone (MGG4-shMYC-shCont) and with CDK18 (MGG4-shMYC-shCDK18 (two independent sequences) (f) or BT74-overexpressing MYC alone (BT74-MYC-Con) and with CDK18 (BT74-MYC-CDK18) (g), with (+) or without (−) Dox. Western blots are shown in Supplementary Fig. 6. Data normalized to control and mean ± SEM, representative of three independent experiments performed in triplicate