Figure 6 | Scientific Reports

Figure 6

From: Selective USP7 inhibition elicits cancer cell killing through a p53-dependent mechanism

Figure 6

XL177A acts through a p53-dependent mechanism. (a) Correlation between relative proliferation profiles of 484 cancer cell lines after XL177A treatment for 5 days or CRISPR KO with the indicated sgRNA. (b) Depmap was queried to determine whether mutations in any of >18,000 genes correlated with XL177A AUC. Only TP53 mutant cell lines displayed significantly altered response relative to WT. (c) Lineages enriched as sensitive (left of 0) or resistant (right of 0) to XL177A in the PRISM data set. (d) Relative Cell Titer Glo luminescence of a panel of TP53-WT (red) or TP53-mutant (black) Ewing Sarcoma cell lines after treatment with XL177A for 3 days. (e) Relative Cell Titer Glo luminescence of TC32 cells expressing the indicated sgRNA after treatment with XL177A for 3 days. (f) Correlation between USP7 DEMETER and AVANA dependency scores in the Broad Depmap portal for TP53-WT (red) and TP53-mutant (black) cell lines. (g) Log10 ratio of A549-FF to A549-sgTP53-Renilla cells after treatment of an initial 1:1 mixture of the two cell lines with the indicated sgRNA for the indicated number of days.

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