{"doi":"10.1016/j.celrep.2022.111066","title":"Reciprocal SOX2 regulation by SMAD1-SMAD3 is critical for anoikis resistance and metastasis in cancer","abstract":"Growth factors in tumor environments are regulators of cell survival and metastasis. Here, we reveal the dichotomy between TGF-β superfamily growth factors BMP and TGF-β/activin and their downstream SMAD effectors. Gene expression profiling uncovers SOX2 as a key contextual signaling node regulated in an opposing manner by BMP2, -4, and -9 and TGF-β and activin A to impact anchorage-independent cell survival. We find that SOX2 is repressed by BMPs, leading to a reduction in intraperitoneal tumor burden and improved survival of tumor-bearing mice. Repression of SOX2 is driven by SMAD1-dependent histone H3K27me3 recruitment and DNA methylation at SOX2's promoter. Conversely, TGF-β, which is elevated in patient ascites, and activin A can promote SOX2 expression and anchorage-independent survival by SMAD3-dependent histone H3K4me3 recruitment. Our findings identify SOX2 as a contextual and contrastingly regulated node downstream of TGF-β members controlling anchorage-independent survival and metastasis in ovarian cancers.","journal":"Cell Reports","year":2022,"id":237114,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":63,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9514,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":825687,"name":"Mehri Monavarian","orcid":"0000-0002-3320-2974","position":1,"is_corresponding":false},{"id":858802,"name":"Kathleen O’Connell","orcid":"0000-0001-6617-8205","position":2,"is_corresponding":false},{"id":396952,"name":"Diego Altomare","orcid":"0000-0002-9126-5703","position":3,"is_corresponding":false},{"id":858475,"name":"Abigail Shelton","orcid":null,"position":4,"is_corresponding":false},{"id":859639,"name":"Shubham Mehta","orcid":null,"position":5,"is_corresponding":false},{"id":340625,"name":"Renata Jaskula‐Sztul","orcid":null,"position":6,"is_corresponding":false},{"id":240808,"name":"Rébécca Phaëton","orcid":"0000-0003-0488-239X","position":7,"is_corresponding":false},{"id":243407,"name":"Mark D. Starr","orcid":null,"position":8,"is_corresponding":false},{"id":596047,"name":"Regina S. Whitaker","orcid":"0000-0003-0310-908X","position":9,"is_corresponding":false},{"id":303,"name":"Andrew Berchuck","orcid":"0000-0002-1940-1467","position":10,"is_corresponding":false},{"id":239530,"name":"Andrew B. Nixon","orcid":"0000-0003-3971-2964","position":11,"is_corresponding":false},{"id":289543,"name":"Rebecca C. Arend","orcid":"0000-0003-2108-3426","position":12,"is_corresponding":false},{"id":587166,"name":"Nam Y. Lee","orcid":"0000-0002-3730-0774","position":13,"is_corresponding":false},{"id":32009,"name":"C. Ryan Miller","orcid":"0000-0002-0096-8762","position":14,"is_corresponding":false},{"id":240809,"name":"Nadine Hempel","orcid":"0000-0002-5574-8783","position":15,"is_corresponding":false},{"id":538103,"name":"Karthikeyan Mythreye","orcid":"0000-0001-5478-0098","position":16,"is_corresponding":false},{"id":858801,"name":"Zainab Shonibare","orcid":"0000-0002-9140-7679","position":0,"is_corresponding":true}],"reference_count":95,"raw_metadata":null,"created_at":"2026-07-19T00:22:08.925400Z","pmid":"35905726","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":[]}