NR2F1 controls tumour cell dormancy via SOX9- and RARβ-driven quiescence programmes.

Abstract	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.
Authors	Maria Soledad Sosa, Falguni Parikh, Alexandre Gaspar Maia, Yeriel Estrada, Almudena Bosch, Paloma Bragado, Esther Ekpin, Ajish George, Yang Zheng, Hung-Ming Lam, Colm Morrissey, Chi-Yeh Chung, Eduardo F Farias, Emily Bernstein, Julio A Aguirre-Ghiso
Journal	Nature communications (Nat Commun) Vol. 6 Pg. 6170 (Jan 30 2015) ISSN: 2041-1723 [Electronic] England
PMID	25636082 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
Chemical References	COUP Transcription Factor I Homeodomain Proteins Receptors, Retinoic Acid SOX9 Transcription Factor
Topics	Animals COUP Transcription Factor I (metabolism) Cell Line, Tumor Fluorescent Antibody Technique Gene Expression Regulation, Neoplastic Homeodomain Proteins (metabolism) Humans Immunohistochemistry Male Mice Mice, Nude Prostatic Neoplasms (metabolism) RNA Interference Receptors, Retinoic Acid (metabolism) SOX9 Transcription Factor (metabolism) Tumor Cells, Cultured

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