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Stratification and therapeutic potential of PML in metastatic breast cancer

Author

Listed:
  • Natalia Martín-Martín

    (CIC bioGUNE, Bizkaia Technology Park)

  • Marco Piva

    (CIC bioGUNE, Bizkaia Technology Park)

  • Jelena Urosevic

    (Oncology Programme, Institute for Research in Biomedicine (IRB-Barcelona))

  • Paula Aldaz

    (Oncology Area, Biodonostia Institute)

  • James D. Sutherland

    (CIC bioGUNE, Bizkaia Technology Park)

  • Sonia Fernández-Ruiz

    (CIC bioGUNE, Bizkaia Technology Park)

  • Leire Arreal

    (CIC bioGUNE, Bizkaia Technology Park)

  • Verónica Torrano

    (CIC bioGUNE, Bizkaia Technology Park)

  • Ana R. Cortazar

    (CIC bioGUNE, Bizkaia Technology Park)

  • Evarist Planet

    (Biostatistics and Bioinformatics Unit, Institute for Research in Biomedicine (IRB-Barcelona)
    School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL))

  • Marc Guiu

    (Oncology Programme, Institute for Research in Biomedicine (IRB-Barcelona))

  • Nina Radosevic-Robin

    (ERTICa Research Group, University of Auvergne EA4677
    Biodiagnostics Laboratory OncoGenAuvergne, Pathology Unit, Jean Perrin Comprehensive Cancer Center)

  • Stephane Garcia

    (Centre de Recherche en Cancérologie de Marseille (CRCM), INSERM UMR 1068, CNRS UMR 7258, Aix-Marseille University and Institut Paoli-Calmettes, Parc Scientifique et Technologique de Luminy)

  • Iratxe Macías

    (CIC bioGUNE, Bizkaia Technology Park)

  • Fernando Salvador

    (Oncology Programme, Institute for Research in Biomedicine (IRB-Barcelona))

  • Giacomo Domenici

    (CIC bioGUNE, Bizkaia Technology Park)

  • Oscar M. Rueda

    (Cancer Research UK Cambridge Institute, University of Cambridge)

  • Amaia Zabala-Letona

    (CIC bioGUNE, Bizkaia Technology Park)

  • Amaia Arruabarrena-Aristorena

    (CIC bioGUNE, Bizkaia Technology Park)

  • Patricia Zúñiga-García

    (CIC bioGUNE, Bizkaia Technology Park)

  • Alfredo Caro-Maldonado

    (CIC bioGUNE, Bizkaia Technology Park)

  • Lorea Valcárcel-Jiménez

    (CIC bioGUNE, Bizkaia Technology Park)

  • Pilar Sánchez-Mosquera

    (CIC bioGUNE, Bizkaia Technology Park)

  • Marta Varela-Rey

    (CIC bioGUNE, Bizkaia Technology Park
    Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd))

  • Maria Luz Martínez-Chantar

    (CIC bioGUNE, Bizkaia Technology Park
    Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd))

  • Juan Anguita

    (CIC bioGUNE, Bizkaia Technology Park
    IKERBASQUE, Basque foundation for science)

  • Yasir H. Ibrahim

    (Experimental Therapeutics Group, Vall d'Hebron University Hospital
    Weill Cornell Medicine)

  • Maurizio Scaltriti

    (Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center)

  • Charles H. Lawrie

    (Oncology Area, Biodonostia Institute
    IKERBASQUE, Basque foundation for science)

  • Ana M. Aransay

    (CIC bioGUNE, Bizkaia Technology Park
    Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd))

  • Juan L. Iovanna

    (Centre de Recherche en Cancérologie de Marseille (CRCM), INSERM UMR 1068, CNRS UMR 7258, Aix-Marseille University and Institut Paoli-Calmettes, Parc Scientifique et Technologique de Luminy)

  • Jose Baselga

    (Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center)

  • Carlos Caldas

    (Cancer Research UK Cambridge Institute, University of Cambridge)

  • Rosa Barrio

    (CIC bioGUNE, Bizkaia Technology Park)

  • Violeta Serra

    (Experimental Therapeutics Group, Vall d'Hebron University Hospital)

  • Maria dM Vivanco

    (CIC bioGUNE, Bizkaia Technology Park)

  • Ander Matheu

    (Oncology Area, Biodonostia Institute
    IKERBASQUE, Basque foundation for science)

  • Roger R. Gomis

    (Oncology Programme, Institute for Research in Biomedicine (IRB-Barcelona)
    Institució Catalana de Recerca i Estudis Avançats (ICREA))

  • Arkaitz Carracedo

    (CIC bioGUNE, Bizkaia Technology Park
    IKERBASQUE, Basque foundation for science
    University of the Basque Country (UPV/EHU))

Abstract

Patient stratification has been instrumental for the success of targeted therapies in breast cancer. However, the molecular basis of metastatic breast cancer and its therapeutic vulnerabilities remain poorly understood. Here we show that PML is a novel target in aggressive breast cancer. The acquisition of aggressiveness and metastatic features in breast tumours is accompanied by the elevated PML expression and enhanced sensitivity to its inhibition. Interestingly, we find that STAT3 is responsible, at least in part, for the transcriptional upregulation of PML in breast cancer. Moreover, PML targeting hampers breast cancer initiation and metastatic seeding. Mechanistically, this biological activity relies on the regulation of the stem cell gene SOX9 through interaction of PML with its promoter region. Altogether, we identify a novel pathway sustaining breast cancer aggressiveness that can be therapeutically exploited in combination with PML-based stratification.

Suggested Citation

  • Natalia Martín-Martín & Marco Piva & Jelena Urosevic & Paula Aldaz & James D. Sutherland & Sonia Fernández-Ruiz & Leire Arreal & Verónica Torrano & Ana R. Cortazar & Evarist Planet & Marc Guiu & Nina , 2016. "Stratification and therapeutic potential of PML in metastatic breast cancer," Nature Communications, Nature, vol. 7(1), pages 1-13, November.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms12595
    DOI: 10.1038/ncomms12595
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    Cited by:

    1. Sarah Tessier & Omar Ferhi & Marie-Claude Geoffroy & Román González-Prieto & Antoine Canat & Samuel Quentin & Marika Pla & Michiko Niwa-Kawakita & Pierre Bercier & Domitille Rérolle & Marilyn Tirard &, 2022. "Exploration of nuclear body-enhanced sumoylation reveals that PML represses 2-cell features of embryonic stem cells," Nature Communications, Nature, vol. 13(1), pages 1-15, December.

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