Fig. 5: NPM1 loss induces protein synthesis stress.
From: Nucleophosmin supports WNT-driven hyperproliferation and tumor initiation
a, Representative staining for p-4E-BP1 (Thr37/46) on SI tissue sections from ApcloxP/+KrasG12D/+ (n = 6) and ApcloxP/+KrasG12D/+Npm1loxP/loxP (n = 5) animals collected at the endpoint. The red dotted lines indicate intestinal adenomas. b, HALO H-score quantification normalized to the average control value of p-4E-BP1 expression in tumors (left) and crypts (right) of the groups shown in a. c, Representative staining for p-eEF2 (Thr56) on SI tissue sections from ApcloxP/+KrasG12D/+ and ApcloxP/+KrasG12D/+Npm1loxP/loxP animals collected at the endpoint (n = 6 per group). The red dotted lines indicate intestinal adenomas. d, HALO H-score quantification normalized to the average control value of p-eEF2 expression in tumors (left) and crypts (right) of the groups shown in c. e, Representative staining for p-eIF2α (Ser51) on SI tissue sections from ApcloxP/+KrasG12D/+ (n = 4) and ApcloxP/+KrasG12D/+Npm1loxP/loxP (n = 5) animals collected at the endpoint. The red dotted lines indicate intestinal adenomas. f, HALO H-score quantification of p-eIF2α expression in the tumors (left) and crypts (right) of the groups shown in e. g, HALO quantification of p-eIF2α stain intensity in the tumors (left) and crypts (right) of the groups shown in e. h, Enrichment profile for the pathway response to ER stress (from the Gene Ontology Biological Process subset) from the proteomics data. The NES and Padj value were calculated as in Fig. 4d and are shown in the plot. b,d,f, All data were statistically assessed using an unpaired, two-tailed t-test. g, Statistical significance was assessed using multiple two-sided t-tests, with P values adjusted using the Holm-Šidák method. Padj values are shown. The boxes in box plots extend from the 25th to 75th percentile, the whiskers extend to the minimum and maximum values, and the line in every box is plotted at the median. Statistically significant P values are shown in red. a,c, Scale bar, 300 μm. e, Scale bar, 200 μm.
