{"doi":"10.1084/jem.20210836","title":"An NR2F1-specific agonist suppresses metastasis by inducing cancer cell dormancy","abstract":"We describe the discovery of an agonist of the nuclear receptor NR2F1 that specifically activates dormancy programs in malignant cells. The agonist led to a self-regulated increase in NR2F1 mRNA and protein and downstream transcription of a novel dormancy program. This program led to growth arrest of an HNSCC PDX line, human cell lines, and patient-derived organoids in 3D cultures and in vivo. This effect was lost when NR2F1 was knocked out by CRISPR-Cas9. RNA sequencing revealed that agonist treatment induces transcriptional changes associated with inhibition of cell cycle progression and mTOR signaling, metastasis suppression, and induction of a neural crest lineage program. In mice, agonist treatment resulted in inhibition of lung HNSCC metastasis, even after cessation of the treatment, where disseminated tumor cells displayed an NR2F1hi/p27hi/Ki-67lo/p-S6lo phenotype and remained in a dormant single-cell state. Our work provides proof of principle supporting the use of NR2F1 agonists to induce dormancy as a therapeutic strategy to prevent metastasis.","journal":"The Journal of Experimental Medicine","year":2021,"id":149619,"datarank":0.6980940525236285,"base_score":4.653960350157523,"endowment":4.653960350157523,"self_citation_contribution":0.6980940525236285,"citation_network_contribution":0.0,"self_endowment_contribution":0.6980940525236285,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":104,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9584,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":469442,"name":"Roberto Sánchez","orcid":"0000-0002-7805-3597","position":1,"is_corresponding":false},{"id":637416,"name":"Tasrina Rahman","orcid":null,"position":2,"is_corresponding":false},{"id":636375,"name":"Carolina Rodríguez-Tirado","orcid":"0000-0002-3853-7909","position":3,"is_corresponding":false},{"id":636376,"name":"Stefan Moritsch","orcid":"0000-0002-1849-1616","position":4,"is_corresponding":false},{"id":636377,"name":"Alba Rodríguez‐Martínez","orcid":"0000-0002-9652-1550","position":5,"is_corresponding":false},{"id":637417,"name":"Brett A. Miles","orcid":null,"position":6,"is_corresponding":false},{"id":619037,"name":"Eduardo Farias","orcid":"0000-0003-4811-7550","position":7,"is_corresponding":false},{"id":404107,"name":"Mihaly Mezei","orcid":"0000-0003-0294-4307","position":8,"is_corresponding":false},{"id":619036,"name":"Ana Rita Nobre","orcid":"0000-0002-5509-904X","position":9,"is_corresponding":false},{"id":444245,"name":"Deepak Kumar Singh","orcid":"0000-0002-1265-7988","position":10,"is_corresponding":false},{"id":636378,"name":"Nupura Kale","orcid":"0000-0002-3185-8646","position":11,"is_corresponding":false},{"id":636379,"name":"Christoph Sproll","orcid":"0000-0002-8637-9255","position":12,"is_corresponding":false},{"id":636380,"name":"María Soledad Sosa","orcid":"0000-0001-8783-3520","position":13,"is_corresponding":false},{"id":105283,"name":"Julio A. Aguirre‐Ghiso","orcid":"0000-0002-6694-6507","position":14,"is_corresponding":false},{"id":604634,"name":"Bassem D. Khalil","orcid":"0000-0001-8699-6950","position":0,"is_corresponding":true}],"reference_count":61,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:42:56.251607Z","pmid":"34812843","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}