TP53 drives invasion through expression of its ∆133p53β variant

Gilles Gadea, Nikola Arsic, Kenneth Fernandes, Alexandra Diot, Sébastien M. Joruiz, Samer Abdallah, Valerie Meuray, Stéphanie Vinot, Christelle Anguille, Judit Remenyi, Marie P. Khoury, Philip R. Quinlan, Colin A. Purdie, Lee B. Jordan, Frances V. Fuller-Pace, Marion de Toledo, Maïlys Cren, Alastair M. Thompson, Jean-Christophe Bourdon (Lead / Corresponding author), Pierre Roux (Lead / Corresponding author)

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    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 Δ133p53β promotes cancer cell invasion, regardless of TP53 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 TP53. 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 TP53 can promote cancer cell invasion and reciprocally why mutant TP53 gene does not systematically induce cancer progression.
    Original languageEnglish
    Article numbere14734
    Pages (from-to)1-26
    Number of pages26
    JournaleLife
    Volume5
    DOIs
    Publication statusPublished - 15 Sep 2016

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    Gadea, G., Arsic, N., Fernandes, K., Diot, A., Joruiz, S. M., Abdallah, S., Meuray, V., Vinot, S., Anguille, C., Remenyi, J., Khoury, M. P., Quinlan, P. R., Purdie, C. A., Jordan, L. B., Fuller-Pace, F. V., de Toledo, M., Cren, M., Thompson, A. M., Bourdon, J-C., & Roux , P. (2016). TP53 drives invasion through expression of its ∆133p53β variant. eLife, 5, 1-26. [e14734]. https://doi.org/10.7554/eLife.14734