MSK1 regulates luminal cell differentiation and metastatic dormancy in ER + breast cancer

Sylwia Gawrzak, Lorenzo Rinaldi, Sara Gregorio, Enrique J. Arenas, Fernando Salvador, Jelena Urosevic, Cristina Figueras-Puig, Federico Rojo, Ivan Del Barco Barrantes, Juan Miguel Cejalvo, Marta Palafox, Marc Guiu, Antonio Berenguer-Llergo, Aikaterini Symeonidi, Anna Bellmunt, Daniela Kalafatovic, Anna Arnal-Estapé, Esther Fernández, Barbara Müllauer, Rianne GroeneveldKonstantin Slobodnyuk, Camille Stephan-Otto Attolini, Cristina Saura, Joaquín Arribas, Javier Cortes, Ana Rovira, Montse Muñoz, Ana Lluch, Violeta Serra, Joan Albanell, Aleix Prat, Angel R. Nebreda, Salvador Aznar Benitah, Roger R. Gomis

    Research output: Contribution to journalArticleResearchpeer-review

    37 Citations (Scopus)

    Abstract

    © 2018 The Author(s). For many patients with breast cancer, symptomatic bone metastases appear after years of latency. How micrometastatic lesions remain dormant and undetectable before initiating colonization is unclear. Here, we describe a mechanism involved in bone metastatic latency of oestrogen receptor-positive (ER + ) breast cancer. Using an in vivo genome-wide short hairpin RNA screening, we identified the kinase MSK1 as an important regulator of metastatic dormancy in breast cancer. In patients with ER + breast cancer, low MSK1 expression associates with early metastasis. We show that MSK1 downregulation impairs the differentiation of breast cancer cells, increasing their bone homing and growth capacities. MSK1 controls the expression of genes required for luminal cell differentiation, including the GATA3 and FOXA1 transcription factors, by modulating their promoter chromatin status. Our results indicate that MSK1 prevents metastatic progression of ER + breast cancer, suggesting that stratifying patients with breast cancer as high or low risk for early relapse based on MSK1 expression could improve prognosis.
    Original languageEnglish
    Pages (from-to)211-221
    JournalNature Cell Biology
    Volume20
    Issue number2
    DOIs
    Publication statusPublished - 1 Feb 2018

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