RUNX3 depletion induces cellular senescence in an ATM/ATR dependent, but p53-independent manner. RUNX3 depletion induces cellular senescence in an ATM/ATR.

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RUNX3 depletion induces cellular senescence in an ATM/ATR dependent, but p53-independent manner. RUNX3 depletion induces cellular senescence in an ATM/ATR dependent, but p53-independent manner. A, A549 cells were subjected to CONT-KD, RUNX3-KD, or RUNX3/p53-DKD for 3 days. As indicated, cells were pretreated with either vehicle (DMSO), KU-55933 (10 μmol/L), or VE-821 (2 μmol/L) for 2 hours, following which, they were exposed to TGFβ for 48 hours in the presence of the small-molecule inhibitors. Coimmunofluorescence staining was performed with antibodies recognizing pSQ/TQ sites and γH2AX. Zoomed (200%) image of the inset is shown on the right. Percent cells expressing greater than 5 γH2AX foci are indicated within the parentheses. Scale bar, 50 μm. B, For the experiment described in A above, cells were fixed and stained for SA-β-gal enzyme overnight at 37°C. Scale bar, 100 μm. C, SA-β-gal–positive cells (blue) were scored and plotted. Graphs show mean ± SD. Asterisks represent significant differences. *, P < 0.05; **, P < 0.01; ***, P < 0.001; n.s, not significant. Vaidehi Krishnan et al. Cancer Res 2018;78:88-102 ©2018 by American Association for Cancer Research