<i>TP53</i> drives invasion through expression of its Δ133p53β variant.

Abstract

<i>TP53</i> is conventionally thought to prevent cancer formation and progression to metastasis, while mutant <i>TP53</i> has transforming activities. However, in the clinic, <i>TP53</i> mutation status does not accurately predict cancer progression. Here we report, based on clinical analysis corroborated with experimental data, that the p53 isoform Δ133p53β promotes cancer cell invasion, regardless of <i>TP53</i> mutation status. Δ133p53β increases risk of cancer recurrence and death in breast cancer patients. Furthermore Δ133p53β is critical to define invasiveness in a panel of breast and colon cell lines, expressing WT or mutant <i>TP53</i>. Endogenous mutant Δ133p53β depletion prevents invasiveness without affecting mutant full-length p53 protein expression. Mechanistically WT and mutant Δ133p53β induces EMT. Our findings provide explanations to 2 long-lasting and important clinical conundrums: how WT <i>TP53</i> can promote cancer cell invasion and reciprocally why mutant <i>TP53</i> gene does not systematically induce cancer progression.