{"doi":"10.1016/j.celrep.2023.112103","title":"Nitric oxide suppression by secreted frizzled-related protein 2 drives retinoblastoma","abstract":"Retinoblastoma is a cancer of the infant retina primarily driven by loss of the Rb tumor suppressor gene, which is undruggable. Here, we report an autocrine signaling, mediated by secreted frizzled-related protein 2 (SFRP2), which suppresses nitric oxide and enables retinoblastoma growth. We show that coxsackievirus and adenovirus receptor (CXADR) is the cell-surface receptor for SFRP2 in retinoblastoma cells; that CXADR functions as a \"dependence receptor,\" transmitting a growth-inhibitory signal in the absence of SFRP2; and that the balance between SFRP2 and CXADR determines nitric oxide production. Accordingly, high SFRP2 RNA expression correlates with high-risk histopathologic features in retinoblastoma. Targeting SFRP2 signaling by SFRP2-binding peptides or by a pharmacological inhibitor rapidly induces nitric oxide and profoundly inhibits retinoblastoma growth in orthotopic xenograft models. These results reveal a cytokine signaling pathway that regulates nitric oxide production and retinoblastoma cell proliferation and is amenable to therapeutic intervention.","journal":"Cell Reports","year":2023,"id":350820,"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":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9534,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":501214,"name":"Fuchun Zhou","orcid":"0000-0002-9431-7708","position":1,"is_corresponding":false},{"id":502090,"name":"Xiuye Ma","orcid":null,"position":2,"is_corresponding":false},{"id":735924,"name":"Kathryn Bondra","orcid":"0000-0002-7261-3346","position":3,"is_corresponding":false},{"id":502091,"name":"Barron Blackman","orcid":null,"position":4,"is_corresponding":false},{"id":432658,"name":"Susan T. Weintraub","orcid":"0000-0002-8328-7814","position":5,"is_corresponding":false},{"id":238480,"name":"Yidong Chen","orcid":"0000-0001-6806-2185","position":6,"is_corresponding":false},{"id":317491,"name":"Patricia Chévez‐Barrios","orcid":"0000-0001-6275-2660","position":7,"is_corresponding":false},{"id":30173,"name":"Peter J. Houghton","orcid":"0000-0002-2400-8184","position":8,"is_corresponding":false},{"id":1095185,"name":"Brenda L. Gallie","orcid":"0000-0002-9697-9211","position":9,"is_corresponding":false},{"id":493588,"name":"Yuzuru Shiio","orcid":"0000-0002-3391-9086","position":10,"is_corresponding":false},{"id":502089,"name":"Panneerselvam Jayabal","orcid":null,"position":0,"is_corresponding":true}],"reference_count":53,"raw_metadata":null,"created_at":"2026-07-19T01:12:37.409066Z","pmid":"36773293","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":[]}