RARRES3 suppresses breast cancer lung metastasis by regulating adhesion and differentiation

Mònica Morales, Enrique J. Arenas, Jelena Urosevic, Marc Guiu, Esther Fernández, Evarist Planet, Robert Bryn Fenwick, Sonia Fernández-Ruiz, Xavier Salvatella, David Reverter, Arkaitz Carracedo, Joan Massagué, Roger R. Gomis

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41 Citations (Scopus)

Abstract

In estrogen receptor-negative breast cancer patients, metastatic relapse usually occurs in the lung and is responsible for the fatal outcome of the disease. Thus, a better understanding of the biology of metastasis is needed. In particular, biomarkers to identify patients that are at risk of lung metastasis could open the avenue for new therapeutic opportunities. Here we characterize the biological activity of RARRES3, a new metastasis suppressor gene whose reduced expression in the primary breast tumors identifies a subgroup of patients more likely to develop lung metastasis. We show that RARRES3 downregulation engages metastasis-initiating capabilities by facilitating adhesion of the tumor cells to the lung parenchyma. In addition, impaired tumor cell differentiation due to the loss of RARRES3 phospholipase A1/A2 activity also contributes to lung metastasis. Our results establish RARRES3 downregulation as a potential biomarker to identify patients at high risk of lung metastasis who might benefit from a differentiation treatment in the adjuvant programme. © 2014 The Authors. Published under the terms of the CC BY 4.0 license.
Original languageEnglish
Pages (from-to)865-881
JournalEMBO Molecular Medicine
Volume6
Issue number7
DOIs
Publication statusPublished - 1 Jan 2014

Keywords

  • Breast cancer
  • Lung metastasis
  • Metastasis suppressor

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    Morales, M., Arenas, E. J., Urosevic, J., Guiu, M., Fernández, E., Planet, E., Fenwick, R. B., Fernández-Ruiz, S., Salvatella, X., Reverter, D., Carracedo, A., Massagué, J., & Gomis, R. R. (2014). RARRES3 suppresses breast cancer lung metastasis by regulating adhesion and differentiation. EMBO Molecular Medicine, 6(7), 865-881. https://doi.org/10.15252/emmm.201303675