TP53 drives invasion through expression of its Δ133p53β variant

Abstract : TP53 is conventionally thought to prevent cancer formation and progression to metastasis, while mutant TP53 has transforming activities. However, in the clinic, TP53 mutation status does not accurately predict cancer progression. Here we report, based on clinical analysis corroborated with experimental data, that the p53 isoform D133p53b promotes cancer cell invasion, regardless of TP53 mutation status. D133p53b increases risk of cancer recurrence and death in breast cancer patients. Furthermore D133p53b is critical to define invasiveness in a panel of breast and colon cell lines, expressing WT or mutant TP53. Endogenous mutant D133p53b depletion prevents invasiveness without affecting mutant full-length p53 protein expression. Mechanistically WT and mutant D133p53b induces EMT. Our findings provide explanations to 2 long-lasting and important clinical conundrums: how WT TP53 can promote cancer cell invasion and reciprocally why mutant TP53 gene does not systematically induce cancer progression.