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Nat Cell Biol. 2018 Feb;20(2):211-221. doi: 10.1038/s41556-017-0021-z. Epub 2018 Jan 22.

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

Author information

1
Oncology Program, Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Spain.
2
CIBERONC, Madrid, Spain.
3
Cancer Research Program, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain.
4
Pathology Department, IIS-Fundación Jimenez Diaz, Madrid, Spain.
5
Translational Genomics and Targeted Therapeutics, Institut d'Investigacions Biomèdiques Pi i Sunyer-IDIBAPS, Barcelona, Spain.
6
Experimental Therapeutics, Vall d'Hebron Insitute of Oncology, Barcelona, Spain.
7
Biostatistics and Bioinformatics Unit, Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Spain.
8
Department of Pathology, Yale University School of Medicine, Yale, CT, USA.
9
Department of Oncology, Vall d'Hebrón University Hospital, Barcelona, Spain.
10
Vall d'Hebron Institute of Oncology, Barcelona, Spain.
11
Universitat Autònoma de Barcelona, Bellaterra, Spain.
12
ICREA, Institució Catalana de Recerca i Estudis Avançats, Barcelona, Spain.
13
Ramon y Cajal University Hospital, Madrid, Spain.
14
Medical Oncology Service, Hospital del Mar, Barcelona, Spain.
15
Department of Oncology, Hospital Clinic de Barcelona, Barcelona, Spain.
16
Department of Oncology and Hematology, Hospital Clínico Universitario, Valencia, Spain.
17
University of Valencia, Valencia, Spain.
18
INCLIVA, Instituto de Investigación Sanitaria, Valencia, Spain.
19
Universitat Pompeu Fabra, Barcelona, Spain.
20
Oncology Program, Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Spain. roger.gomis@irbbarcelona.org.
21
CIBERONC, Madrid, Spain. roger.gomis@irbbarcelona.org.
22
ICREA, Institució Catalana de Recerca i Estudis Avançats, Barcelona, Spain. roger.gomis@irbbarcelona.org.
23
Universitat de Barcelona, Barcelona, Spain. roger.gomis@irbbarcelona.org.

Abstract

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.

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PMID:
29358704
DOI:
10.1038/s41556-017-0021-z
[Indexed for MEDLINE]

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