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NR2F1 controls tumour cell dormancy via SOX9- and RARβ-driven quiescence programmes
Open accessAbstract
Metastases can originate from disseminated tumour cells (DTCs), which may be dormant for years before reactivation. Here we find that the orphan nuclear receptor NR2F1 is epigenetically upregulated in experimental head and neck squamous cell carcinoma (HNSCC) dormancy models and in DTCs from prostate cancer patients carrying dormant disease for 7–18 years. NR2F1-dependent dormancy is recapitulated by a co-treatment with the DNA-demethylating agent 5-Aza-C and retinoic acid across various cancer types. NR2F1-induced quiescence is dependent on SOX9, RARβ and CDK inhibitors. Intriguingly, NR2F1 induces global chromatin repression and the pluripotency gene NANOG, which contributes to dormancy of DTCs in the bone marrow. When NR2F1 is blocked in vivo, growth arrest or survival of dormant DTCs is interrupted in different organs. We conclude that NR2F1 is a critical node in dormancy induction and maintenance by integrating epigenetic programmes of quiescence and survival in DTCs. Tumour cells disseminated from the primary tumour can remain dormant for years before initiating metastases. Here Sosa et al.show that the orphan nuclear receptor NR2F1 can be induced by bone marrow cues and by epigenetic drugs to promote quiescence and tumour cell dormancy in several cancer types.
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Self-citation
Metadata
- Authors
- Sosa, M. S., Parikh, F., Maia, A. G., Estrada, Y., Bosch, A., Bragado, P., Ekpin, E., George, A., Zheng, Y., Lam, H.-M., Morrissey, C., Chung, C.-Y., Farias, E. F., Bernstein, E., & Aguirre-Ghiso, J. A.
- Venue
- Nature Communications
- Published
- 2015-01-30
- Volume
- 6
- Issue
- 1
- Pages
- 6170-6170
- ISSN
- 2041-1723 (ISSN-L)
- OpenAlex
- W2115900736
- Cited by
- 355
- References
- 49
- FWCI
- 8.06
- Type
- journal article
- Language
- en
- Open access
- gold
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