Fig. 2: SHOC2 genetic validation in cancer models.
From: Targeting the SHOC2–RAS interaction in RAS-mutant cancers
a, Scatter plot showing the mean difference (x axis) and significance (y axis; P-values are Benjamini–Hochberg corrected for multiple testing based on a two-sided Mann–Whitney U-test) of DepMap scores in cell lines with RAS mutations (Q61 on the left, G12 on the right). b, Box-plot (median, first and third quartiles are shown with whiskers extending to the 95th percentile) of DepMap score for the indicated genes in cell lines with the indicated RAS mutations. P-values obtained by two-sided Wilcoxon t-test (Q61, n = 60; G12, n = 82). c, Quantification of colony assays for the indicated cell models with doxycycline (dox)-inducible shRNAs treated with dox (+dox) or DMSO (−dox) (mean ± s.d., n = 3 independent experiments). Significance was determined using a two-tailed t-test (*P < 0.05, **P < 0.005, ***P < 0.001). d, Lysates from IPC298 lines with the indicated dox-inducible shRNAs treated with dox (+) or DMSO (−) were immunoblotted with the indicated antibodies. A representative image of three independent experiments is shown. e, Effect of shSHOC2, shNRAS or shControl on the expression of the indicated genes in the UACC275, IPC298 and HEPG2 cell lines. f, Left, MUGMEL2 xenograft growth with or without dox induction of the indicated shRNAs (mean ± s.e.m., n = 6 mice per group). Significance was determined using a one-way ANOVA with Tukey’s multiple-comparison test (***P = 0.0003, ****P < 0.0001). Right, change in tumour volume after 14 days of treatment is presented as a waterfall plot of individual tumours (n = 6 mice per group). Significance was determined by two-tailed unpaired t-test (****P < 0.0001). g, Pearson correlation of global gene expression log2FCs. h, Change in mRNA expression of the indicated RAS/MAPK-induced genes and control housekeeping gene (RPS14) between KD conditions in the tumours from Extended Data Fig. 2d. shSC2, shSHOC2; shNT, non-targeting shRNA; P-values were calculated using the DESeq2 Wald test and are FDR corrected).
