Cooperation of mutant RNF43 with active Ras establishes Wnt-Ras-p53 axis.a Induction of p53 and p21 protein was examined by immunoblotting (IB) with Eto treatment. Expression of p53 and p21 in empty vector-transfected NC cells with DMSO treatment was set to 1. Bar graphs and error bars represent mean ± sd. Red circles indicate individual values of each sample. Asterisks indicate significant differences from NC cells stimulated with Eto (P < 0.05, one-way ANOVA, n = 3 biological replicates). ND indicates no significant difference. b, c Prognosis of patients with colorectal tumour that carry genetic mutations in RNF43 with or without KRAS (b) or in RNF43 with or without TP53 (c) is shown. Sample number and P value determined by log-rank test (b, c) with Holm adjustment for multiple comparisons (b) are indicated in each graph. d Schematic of biological role of RNF43 oncogenic mutations in multi-step tumorigenesis. Oncogenic RNF43 mutants that promote Wnt signalling and inhibit the p53 pathway cooperate with activating Ras mutations to complete all the steps of multi-step colorectal tumorigenesis.
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