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| Status |
Public on Nov 13, 2017 |
| Title |
MSK1 regulates luminal cell differentiation and metastatic dormancy in breast cancer |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
For many breast cancer (BCa) patients, symptomatic bone metastases appear after years or even decades of latency. How metastatic cells disseminate, and how micrometastatic lesions remain dormant and undetectable yet initiate colonization, are major questions in cancer research. Here we identify and functionally analyse a molecular mechanism involved in bone metastatic latency of estrogen receptor–positive (ER)+ BCa. We developed an in vivo loss-of-function, genome-wide shRNA screening to identify genes relevant for long-latent relapse in BCa. This screen revealed the kinase MSK1 as an important regulator of metastatic dormancy. Importantly, low MSK1 expression associates with early metastasis in ER+ BCa patients. Reduced MSK1 levels impaired cellular differentiation and increased the bone homing and growth capacity of metastatic cells. MSK1 modulates chromatin status at promoters to regulate the expression of luminal differentiation genes, including those for the GATA-3 and FOXA1 transcription factors, which prevent the progression of ER+ BCa towards metastasis. Our results identify the regulation of luminal cell differentiation by MSK1 via modulation of chromatin remodelling to be a key mechanism for controlling metastatic dormancy in BCa. We propose that MSK1 could be a useful marker for stratifying BCa patients as high- or low-risk for early relapse, allowing patients to receive appropriate treatments.
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| Overall design |
4 samples were analysed, 2 shControl samples for each of the phosphorylation sites (S10P and S28P) and 2 samples of the shMSK1 for each of the phosphorylation sites. In addition, for the shControl and shMSK1 Input-DNA was used.
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| Contributor(s) |
Gawrzak S, Rinaldi L, Arenas EJ, Salvador F, Rojo F, del Barco Barrantes I, Cejalvo J, Palafox M, Guiu M, Berenguer-Llergo A, Symeonidi A, Stephan-Otto Attolini C, Urosevic J, Bellmunt A, Gregorio S, Kalafatovic D, Arnal-Estapé A, Müllauer B, Groeneveld R, Serra C, Cortes J, Rovira A, Muñoz M, Lluch A, Arribas J, Serra V, Albanell J, Prat A, Nebreda AR, Aznar-Benitah S, Gomis RR |
| Citation(s) |
29358704 |
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| Submission date |
Jun 21, 2017 |
| Last update date |
Jul 25, 2021 |
| Contact name |
Aikaterini Symeonidi |
| E-mail(s) |
ksymeonidh@gmail.com
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| Organization name |
Institut for Research in Biomedicine (IRB-Barcelona)
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| Department |
Oncology
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| Lab |
Stem cells and Cancer Lab
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| Street address |
Baldiri i Reixac, 10
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| City |
Barcelona |
| State/province |
Barcelona |
| ZIP/Postal code |
08028 |
| Country |
Spain |
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| Platforms (1) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA391297 |
| SRA |
SRP110021 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE100306_RAW.tar |
2.0 Gb |
(http)(custom) |
TAR (of BEDGRAPH) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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