Open AccessRARRES 3 suppresses breast cancer lung metastasis by regulating adhesion and differentiation
Author(s) -
Morales Mònica,
Arenas Enrique J,
Urosevic Jelena,
Guiu Marc,
Fernández Esther,
Planet Evarist,
Fenwick Robert Bryn,
FernándezRuiz Sonia,
Salvatella Xavier,
Reverter David,
Carracedo Arkaitz,
Massagué Joan,
Gomis Roger R
Publication year - 2014
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.15252/emmm.201303675
Subject(s) - metastasis , breast cancer , downregulation and upregulation , lung cancer , lung , cancer research , medicine , estrogen receptor , oncology , cancer , pathology , biology , gene , biochemistry
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 RARRES 3 , 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 RARRES 3 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 RARRES 3 phospholipase A 1/ A 2 activity also contributes to lung metastasis. Our results establish RARRES 3 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.