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EMBO Mol Med. 2014 May 27;6(7):865-81. doi: 10.15252/emmm.201303675.

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

Author information

  • 1Oncology Program, Institute for Research in Biomedicine (IRB Barcelona), Barcelona, Spain.
  • 2Biostatistics and Bioinformatics Unit, Institute for Research in Biomedicine (IRB Barcelona), Barcelona, Spain.
  • 3Joint BSC-IRB Research Programme in Computational Biology, Institute for Research in Biomedicine (IRB Barcelona), Barcelona, Spain.
  • 4CIC bioGUNE Bizkaia Tecnology park, Derio, Spain.
  • 5Joint BSC-IRB Research Programme in Computational Biology, Institute for Research in Biomedicine (IRB Barcelona), Barcelona, Spain Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain.
  • 6Departament de Bioquímica i de Biologia Molecular, Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, Bellaterra, Spain.
  • 7CIC bioGUNE Bizkaia Tecnology park, Derio, Spain Biochemistry and Molecular Biology Department, University of the Basque Country (UPV/EHU), Bilbao, Spain Ikerbasque Basque Foundation for Science, Bilbao, Spain.
  • 8Cancer Biology and Genetics Program, Memorial Sloan-Kettering Cancer Center, New York, NY, USA Howard Hughes Medical Institute, Chevy Chase, MD, USA.
  • 9Oncology Program, Institute for Research in Biomedicine (IRB Barcelona), Barcelona, Spain Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain roger.gomis@irbbarcelona.org.

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.

KEYWORDS:

breast cancer; lung metastasis; metastasis suppressor

PMID:
24867881
[PubMed - indexed for MEDLINE]
PMCID:
PMC4119352
Free PMC Article
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