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RARRES3 suppresses breast cancer lung metastasis by regulating adhesion and differentiation.

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.
AuthorsMònica 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
JournalEMBO molecular medicine (EMBO Mol Med) Vol. 6 Issue 7 Pg. 865-81 (Jul 2014) ISSN: 1757-4684 [Electronic] England
PMID24867881 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright© 2014 The Authors. Published under the terms of the CC BY 4.0 license.
Chemical References
  • PLAAT4 protein, human
  • Receptors, Retinoic Acid
Topics
  • Animals
  • Breast (metabolism, pathology)
  • Breast Neoplasms (genetics, metabolism, pathology)
  • Cell Adhesion
  • Cell Differentiation
  • Cell Line, Tumor
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lung (metabolism, pathology)
  • Lung Neoplasms (genetics, metabolism, pathology, secondary)
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Models, Molecular
  • Receptors, Retinoic Acid (genetics, metabolism)

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