title: The p53 isoform Δ133p53β promotes cancer stem cell potential.
abstract: Cancer stem cells (CSC) are responsible for cancer chemoresistance and metastasis formation. Here we report that Δ133p53β, a TP53 splice variant, enhanced cancer cell stemness in MCF-7 breast cancer cells, while its depletion reduced it. Δ133p53β stimulated the expression of the key pluripotency factors SOX2, OCT3/4, and NANOG. Similarly, in highly metastatic breast cancer cells, aggressiveness was coupled with enhanced CSC potential and Δ133p53β expression. Like in MCF-7 cells, SOX2, OCT3/4, and NANOG expression were positively regulated by Δ133p53β in these cells. Finally, treatment of MCF-7 cells with etoposide, a cytotoxic anti-cancer drug, increased CSC formation and SOX2, OCT3/4, and NANOG expression via Δ133p53, thus potentially increasing the risk of cancer recurrence. Our findings show that Δ133p53β supports CSC potential. Moreover, they indicate that the TP53 gene, which is considered a major tumor suppressor gene, also acts as an oncogene via the Δ133p53β isoform.
authors.affiliation: Centre National de la Recherche Scientifique, UMR 5237, Centre de Recherche en Biochimie Macromoléculaire, Université Montpellier, 1919 route de Mende, 34293 Montpellier Cedex 5, France.
authors.forename: Nikola
authors.initials: N
authors.lastname: Arsic
authors.affiliation: Centre National de la Recherche Scientifique, UMR 5237, Centre de Recherche en Biochimie Macromoléculaire, Université Montpellier, 1919 route de Mende, 34293 Montpellier Cedex 5, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Gadea
authors.affiliation: Centre National de la Recherche Scientifique, UMR5203, Institut de Génomique Fonctionnelle, Institut National de la Santé et de la Recherche Médicale, U661, Université Montpellier, route de Cardonille, 34094 Montpellier, France.
authors.forename: E Louise
authors.initials: EL
authors.lastname: Lagerqvist
authors.affiliation: Plateforme Imagerie du Petit Animal de Montpellier (IPAM), Institut de Recherche en Cancérologie de Montpellier Inserm U896, Université Montpellier, ICM Val d'Aurelle Campus Val d'Aurelle, 208 Rue des Apothicaires, 34298 Montpellier Cedex 5, France.
authors.forename: Muriel
authors.initials: M
authors.lastname: Busson
authors.affiliation: Eurobiodev, 2040 avenue du Père Soulas, 34090 Montpellier, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Cahuzac
authors.affiliation: Eurofins Cerep, Le bois L'Evèque, 86600 Celle L'Evescault, France.
authors.forename: Carsten
authors.initials: C
authors.lastname: Brock
authors.affiliation: Department of Pathology, University of Melbourne, Parkville, VIC 3010, Australia.
authors.forename: Frederic
authors.initials: F
authors.lastname: Hollande
authors.affiliation: Centre National de la Recherche Scientifique, UMR 5237, Centre de Recherche en Biochimie Macromoléculaire, Université Montpellier, 1919 route de Mende, 34293 Montpellier Cedex 5, France.
authors.forename: Veronique
authors.initials: V
authors.lastname: Gire
authors.affiliation: Centre National de la Recherche Scientifique, UMR5203, Institut de Génomique Fonctionnelle, Institut National de la Santé et de la Recherche Médicale, U661, Université Montpellier, route de Cardonille, 34094 Montpellier, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Pannequin
authors.affiliation: Centre National de la Recherche Scientifique, UMR 5237, Centre de Recherche en Biochimie Macromoléculaire, Université Montpellier, 1919 route de Mende, 34293 Montpellier Cedex 5, France. Electronic address: pierre.roux@crbm.cnrs.fr.
authors.forename: Pierre
authors.initials: P
authors.lastname: Roux
mesh_terms: D017398:Alternative Splicing; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D000066673:Cell Self Renewal / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D061986:MCF-7 Cells; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D059368:RNA Isoforms; D018874:Spheroids, Cellular; D014157:Transcription Factors / Q000235:genetics; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D059368:RNA Isoforms; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53