title: 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: Division of Hematology and Oncology, Department of Medicine, Mount Sinai School of Medicine, New York, New York 10029, USA.
authors: Maria Soledad
authors: MS
authors: Sosa
authors: 1] Division of Hematology and Oncology, Department of Medicine, Mount Sinai School of Medicine, New York, New York 10029, USA [2] Department of Otolaryngology, Mount Sinai School of Medicine, New York, New York 10029, USA.
authors: Falguni
authors: F
authors: Parikh
authors: Department of Oncological Sciences, Mount Sinai School of Medicine, New York, New York 10029, USA.
authors: Alexandre Gaspar
authors: AG
authors: Maia
authors: Division of Hematology and Oncology, Department of Medicine, Mount Sinai School of Medicine, New York, New York 10029, USA.
authors: Yeriel
authors: Y
authors: Estrada
authors: Division of Hematology and Oncology, Department of Medicine, Mount Sinai School of Medicine, New York, New York 10029, USA.
authors: Almudena
authors: A
authors: Bosch
authors: Division of Hematology and Oncology, Department of Medicine, Mount Sinai School of Medicine, New York, New York 10029, USA.
authors: Paloma
authors: P
authors: Bragado
authors: Division of Hematology and Oncology, Department of Medicine, Mount Sinai School of Medicine, New York, New York 10029, USA.
authors: Esther
authors: E
authors: Ekpin
authors: Division of Hematology and Oncology, Department of Medicine, Mount Sinai School of Medicine, New York, New York 10029, USA.
authors: Ajish
authors: A
authors: George
authors: Department of Otolaryngology, Mount Sinai School of Medicine, New York, New York 10029, USA.
authors: Yang
authors: Y
authors: Zheng
authors: Department of Urology, University of Washington, Seattle, Washington, WA 98195, USA.
authors: Hung-Ming
authors: HM
authors: Lam
authors: Department of Urology, University of Washington, Seattle, Washington, WA 98195, USA.
authors: Colm
authors: C
authors: Morrissey
authors: Department of Oncological Sciences, Mount Sinai School of Medicine, New York, New York 10029, USA.
authors: Chi-Yeh
authors: CY
authors: Chung
authors: 1] Division of Hematology and Oncology, Department of Medicine, Mount Sinai School of Medicine, New York, New York 10029, USA [2] Tisch Cancer Institute, Mount Sinai School of Medicine, New York, New York 10029, USA.
authors: Eduardo F
authors: EF
authors: Farias
authors: 1] Department of Oncological Sciences, Mount Sinai School of Medicine, New York, New York 10029, USA [2] Tisch Cancer Institute, Mount Sinai School of Medicine, New York, New York 10029, USA [3] Black Family Stem Cell Institute, Mount Sinai School of Medicine, New York, New York 10029, USA.
authors: Emily
authors: E
authors: Bernstein
authors: 1] Division of Hematology and Oncology, Department of Medicine, Mount Sinai School of Medicine, New York, New York 10029, USA [2] Department of Otolaryngology, Mount Sinai School of Medicine, New York, New York 10029, USA [3] Tisch Cancer Institute, Mount Sinai School of Medicine, New York, New York 10029, USA [4] Black Family Stem Cell Institute, Mount Sinai School of Medicine, New York, New York 10029, USA.
authors: Julio A
authors: JA
authors: Aguirre-Ghiso
mesh_terms: D000818:Animals; D051838:COUP Transcription Factor I / Q000378:metabolism*; D045744:Cell Line, Tumor; D005455:Fluorescent Antibody Technique; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008819:Mice, Nude; D011471:Prostatic Neoplasms / Q000378:metabolism; D034622:RNA Interference; D018168:Receptors, Retinoic Acid / Q000378:metabolism*; D055758:SOX9 Transcription Factor / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D051838:COUP Transcription Factor I; D018398:Homeodomain Proteins; D018168:Receptors, Retinoic Acid; D055758:SOX9 Transcription Factor
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