TP53 drives invasion through expression of its Δ133p53β variant

Gilles Gadea (1) , Nikola Arsic (2) , Kenneth Fernandes (3) , Alexandra Diot (4) , Sébastien Joruiz (5) , Samer Abdallah (1) , Valerie Meuray (4) , Stéphanie Vinot (1) , Christelle Anguille (1) , Judit Remenyi (5) , Marie P. Khoury (6) , Philip Quinlan (7) , Colin Purdie (8) , Lee Jordan (9) , Frances Fuller-Pace (5) , Marion de Toledo (1) , Maïlys Cren (10) , Alastair Thompson (11) , Jean-Christophe Bourdon (4) , Pierre Roux (12)

1 CRBM - Centre de recherche en Biologie cellulaire de Montpellier
2 IGMM - Institut de Génétique Moléculaire de Montpellier
3 Centre for Oncology and Molecular Medicine
4 Centre of Oncology and Molecular Medicine
5 University of Dundee
6 I2MR - Institut de médecine moléculaire de Rangueil
7 Department of Surgery and Molecular Oncology
8 Department of Pathology [Dundee]
9 Dundee Cancer Center
10 Cellules souches normales et cancéreuses
11 Department of Breast Surgical Oncology [Houston]
12 LIST (CEA) - Laboratoire d'Intégration des Systèmes et des Technologies

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.

Domaines: Génomique, Transcriptomique et Protéomique [q-bio.GN]; Cancer

Gilles Gadea, Nikola Arsic, Kenneth Fernandes, Alexandra Diot, Sébastien Joruiz, et al.. TP53 drives invasion through expression of its Δ133p53β variant. eLife, 2016, 5, pp.e14734. ⟨10.7554/eLife.14734⟩. ⟨hal-01703040⟩