RARRES3 suppresses breast cancer lung metastasis by regulating adhesion and differentiation Journal Article


Authors: 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.
Article Title: 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. © 2014 The Authors. Published under the terms of the CC BY 4.0 license.
Keywords: immunohistochemistry; vasculotropin; controlled study; human tissue; protein expression; unclassified drug; histopathology; nonhuman; protein function; animal cell; mouse; animal tissue; apoptosis; breast cancer; animal experiment; animal model; cell differentiation; enzyme activity; collagen type 1; cancer inhibition; lung metastasis; messenger rna; down regulation; catalysis; estrogen receptor; tumor suppressor protein; cell adhesion; phospholipase a2; short hairpin rna; fibronectin; vimentin; blood vessel permeability; interferon regulatory factor 5; anoikis; human; female; priority journal; article; peroxisome proliferator activated receptor; metastasis suppressor; phospholipase a1; rarres3 protein
Journal Title: EMBO Molecular Medicine
Volume: 6
Issue: 7
ISSN: 1757-4676
Publisher: Wiley Blackwell  
Date Published: 2014-07-01
Start Page: 865
End Page: 881
Language: English
DOI: 10.15252/emmm.201303675
PROVIDER: scopus
PUBMED: 24867881
PMCID: PMC4119352
DOI/URL:
Notes: Export Date: 1 August 2014 -- Source: Scopus
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  1. Joan Massague
    361 Massague