title: TP53drives invasion through expression of its Δ133p53β variant.
abstract: TP53is conventionally thought to prevent cancer formation and progression to metastasis, while mutantTP53has transforming activities. However, in the clinic,TP53mutation 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 ofTP53mutation 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 mutantTP53. 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 WTTP53can promote cancer cell invasion and reciprocally why mutantTP53gene does not systematically induce cancer progression.
authors.affiliation: UM 134 Processus Infectieux en Milieu Insulaire Tropical (PIMIT), INSERM U1187, CNRS UMR9192, IRD UMR249, Université de la Réunion, Sainte Clotilde, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Gadea
authors.affiliation: Université Montpellier, Montpellier, France.|CRBM, CNRS, Centre de Recherche de Biologie cellulaire de Montpellier, Montpellier, France.
authors.forename: Nikola
authors.initials: N
authors.lastname: Arsic
authors.affiliation: Division of Cancer Research, University of Dundee, Ninewells Hospital and Medical School, Dundee, United Kingdom.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Fernandes
authors.affiliation: Division of Cancer Research, University of Dundee, Ninewells Hospital and Medical School, Dundee, United Kingdom.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Diot
authors.affiliation: Division of Cancer Research, University of Dundee, Ninewells Hospital and Medical School, Dundee, United Kingdom.
authors.forename: Sébastien M
authors.initials: SM
authors.lastname: Joruiz
authors.affiliation: Université Montpellier, Montpellier, France.|CRBM, CNRS, Centre de Recherche de Biologie cellulaire de Montpellier, Montpellier, France.
authors.forename: Samer
authors.initials: S
authors.lastname: Abdallah
authors.affiliation: Division of Cancer Research, University of Dundee, Ninewells Hospital and Medical School, Dundee, United Kingdom.
authors.forename: Valerie
authors.initials: V
authors.lastname: Meuray
authors.affiliation: Université Montpellier, Montpellier, France.|CRBM, CNRS, Centre de Recherche de Biologie cellulaire de Montpellier, Montpellier, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Vinot
authors.affiliation: Université Montpellier, Montpellier, France.|CRBM, CNRS, Centre de Recherche de Biologie cellulaire de Montpellier, Montpellier, France.
authors.forename: Christelle
authors.initials: C
authors.lastname: Anguille
authors.affiliation: Division of Cancer Research, University of Dundee, Ninewells Hospital and Medical School, Dundee, United Kingdom.
authors.forename: Judit
authors.initials: J
authors.lastname: Remenyi
authors.affiliation: Division of Cancer Research, University of Dundee, Ninewells Hospital and Medical School, Dundee, United Kingdom.
authors.forename: Marie P
authors.initials: MP
authors.lastname: Khoury
authors.affiliation: Division of Cancer Research, University of Dundee, Ninewells Hospital and Medical School, Dundee, United Kingdom.
authors.forename: Philip R
authors.initials: PR
authors.lastname: Quinlan
authors.affiliation: Division of Cancer Research, University of Dundee, Ninewells Hospital and Medical School, Dundee, United Kingdom.
authors.forename: Colin A
authors.initials: CA
authors.lastname: Purdie
authors.affiliation: Division of Cancer Research, University of Dundee, Ninewells Hospital and Medical School, Dundee, United Kingdom.
authors.forename: Lee B
authors.initials: LB
authors.lastname: Jordan
authors.affiliation: Division of Cancer Research, University of Dundee, Ninewells Hospital and Medical School, Dundee, United Kingdom.
authors.forename: Frances V
authors.identifier: http://orcid.org/0000-0001-5859-2932
authors.initials: FV
authors.lastname: Fuller-Pace
authors.affiliation: Université Montpellier, Montpellier, France.|CNRS, Institut de Génétique Moléculaire de Montpellier, Montpellier, France.
authors.forename: Marion
authors.initials: M
authors.lastname: de Toledo
authors.affiliation: Université Montpellier, Montpellier, France.|IRB, Institut de Recherche en Biothérapie, Montpellier, France.
authors.forename: Maïlys
authors.initials: M
authors.lastname: Cren
authors.affiliation: Division of Cancer Research, University of Dundee, Ninewells Hospital and Medical School, Dundee, United Kingdom.|Department of Surgical Oncology, MD Anderson Cancer Centre, Houston, United States.
authors.forename: Alastair M
authors.initials: AM
authors.lastname: Thompson
authors.affiliation: Division of Cancer Research, University of Dundee, Ninewells Hospital and Medical School, Dundee, United Kingdom.
authors.forename: Jean-Christophe
authors.identifier: http://orcid.org/0000-0003-4623-9386
authors.initials: JC
authors.lastname: Bourdon
authors.affiliation: Université Montpellier, Montpellier, France.|CRBM, CNRS, Centre de Recherche de Biologie cellulaire de Montpellier, Montpellier, France.
authors.forename: Pierre
authors.identifier: http://orcid.org/0000-0003-0671-5413
authors.initials: P
authors.lastname: Roux
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009154:Mutation; D009361:Neoplasm Invasiveness / Q000235:genetics; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000473:pathology; D020033:Protein Isoforms / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D020033:Protein Isoforms; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53
keywords: EMT; cancer biology; cancer invasion; human; p53 isoforms; survival