RARRES3 suppresses breast cancer lung metastasis by regulating adhesion and differentiation

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 me...

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Detalles Bibliográficos
Autores: Morales, Mònica, Arenas, Enrique J.|||0000-0001-7076-2666, Urosevic, Jelena, Guiu, Marc|||0000-0002-7083-986X, Fernández Mostaza, Esther|||0000-0002-2335-0674, Planet, Evarist, Fenwick, Robert Bryn, Fernández Ruiz, Sonia, Salvatella, Xavier|||0000-0002-8371-4185, Reverter Cendrós, David|||0000-0002-5347-0992, Carracedo, Arkaitz|||0000-0001-5957-1260, Massagué, Joan, Gomis, Roger R.|||0000-0001-6473-2858
Tipo de recurso: artículo
Fecha de publicación:2014
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:185044
Acceso en línea:https://ddd.uab.cat/record/185044
https://dx.doi.org/urn:doi:10.15252/emmm.201303675
Access Level:acceso abierto
Palabra clave:Breast cancer
Lung metastasis
Metastasis suppressor
Descripción
Sumario: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.