Extended Data Fig. 5: NPM1 is upregulated and necessary for WNT-driven tumourigenesis.
From: Nucleophosmin supports WNT-driven hyperproliferation and tumor initiation
a, Representative micrographs of NPM1-stained normal intestinal tissue sections and tumours from Apcfl/+ (n = 3) (high WNT-driven tumours) and BrafV600E/+Alk5fl/fl (n = 6) (low WNT-driven tumours) mice harvested at clinical endpoint. b, c, NPM1 staining HALO H-score quantification of the groups shown in (a), normalised to the mean normal epithelium value. d, e, Anxa1 ISH in proximal colon tissue sections from Villin-CreER-T2 (n = 3) sampled 10 days, Villin-CreER-T2BrafLSL-V637E/+(n = 4) and Villin-CreER-T2BrafLSL-V637E/+Npm1fl/fl (n = 4) sampled 7 days post-induction, and HALO quantification shown in (e). Data statistically assessed by one-way ANOVA followed by Tukey’s multiple comparisons test. f, NPM1 expression in wild-type (WT) and mutant (Mut) APC COAD/READ tumours in the TCGA dataset (n = 375). g, h, GSVA score of WNT signatures a and b in WT and Mut APC TCGA COAD/READ tumours. i, Olfm4 ISH and HALO rendering on intestinal tissue sections from Apcfl/fl mice with or without Npm1fl/fl and HALO quantification in (j) (n = 4 per group). k, Tumor number distribution within equidistant proximal to distal SI and colon sections from Apcfl/+ (n = 8) and Apcfl/+Npm1fl/fl (n = 9) mice sampled at clinical endpoint. Data statistically assessed by two-way ANOVA followed by Sidak’s multiple comparisons test. l, Tumor number distribution within equidistant proximal to distal SI and colon sections from Lgr5-CreER-T2Apcfl/fl (n = 11) and Lgr5-CreER-T2Apcfl/flNpm1fl/fl (n = 9) mice sampled at clinical endpoint. Data statistically assessed by two-way ANOVA followed by Sidak’s multiple comparisons test. m, Olfm4 ISH and HALO rendering on intestinal tissue sections from Apcfl/flKrasG12D/+ mice with or without Npm1fl/fl and HALO quantification in (n) (n = 4 per group). o, Tumor number distribution within equidistant proximal to distal SI and colon sections from Apcfl/+KrasG12D/+ (n = 17) and Apcfl/+KrasG12D/+Npm1fl/fl (n = 20) mice sampled at clinical endpoint. Data statistically assessed by two-way ANOVA followed by Sidak’s multiple comparisons test. Bar chart data, mean ± SEM. Boxes in boxplots extend from the 25th to 75th percentiles, whiskers extend to the minimum and maximum values, and the line in every box is plotted at the median. All data in bar charts and boxplots statistically assessed by unpaired two-tailed t tests. Statistically significant p-values are shown in red. Scale bars, 100 μm.
