{"doi":"10.7554/elife.83527","title":"A chronic signaling TGFb zebrafish reporter identifies immune response in melanoma","abstract":"Developmental signaling pathways associated with growth factors such as TGFb are commonly dysregulated in melanoma. Here we identified a human TGFb enhancer specifically activated in melanoma cells treated with TGFB1 ligand. We generated stable transgenic zebrafish with this TGFb Induced Enhancer driving green fluorescent protein ( TIE:EGFP ). TIE:EGFP was not expressed in normal melanocytes or early melanomas but was expressed in spatially distinct regions of advanced melanomas. Single-cell RNA-sequencing revealed that TIE:EGFP + melanoma cells down-regulated interferon response while up-regulating a novel set of chronic TGFb target genes. ChIP-sequencing demonstrated that AP-1 factor binding is required for activation of chronic TGFb response. Overexpression of SATB2 , a chromatin remodeler associated with tumor spreading, showed activation of TGFb signaling in early melanomas. Confocal imaging and flow cytometric analysis showed that macrophages localize to TIE:EGFP + regions and preferentially phagocytose TIE:EGFP + melanoma cells compared to TIE:EGFP - melanoma cells. This work identifies a TGFb induced immune response and demonstrates the need for the development of chronic TGFb biomarkers to predict patient response to TGFb inhibitors.","journal":"eLife","year":2024,"id":464169,"datarank":0.2929734024752081,"base_score":1.791759469228055,"endowment":1.791759469228055,"self_citation_contribution":0.26876392038420827,"citation_network_contribution":0.024209482090999816,"self_endowment_contribution":0.26876392038420827,"citer_contribution":0.024209482090999816,"corpus_percentile":null,"corpus_rank":null,"citation_count":5,"citer_count":3,"citers_with_citation_signal":2,"citers_with_endowment":2,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9483,"is_data_producer":true,"deposit_databanks":{"GEO":["GSE213360"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":550282,"name":"Alexandra Thornock","orcid":"0000-0003-0511-4376","position":1,"is_corresponding":false},{"id":793502,"name":"Julia Barbano","orcid":null,"position":2,"is_corresponding":false},{"id":64921,"name":"Michael E. Xifaras","orcid":"0000-0001-9973-5733","position":3,"is_corresponding":false},{"id":49566,"name":"Chloé S. Baron","orcid":"0000-0001-8351-4768","position":4,"is_corresponding":false},{"id":354451,"name":"Song Yang","orcid":"0000-0002-3064-3141","position":5,"is_corresponding":false},{"id":1295210,"name":"Katherine Koczirka","orcid":null,"position":6,"is_corresponding":false},{"id":49578,"name":"Alicia M. McConnell","orcid":"0000-0002-0984-4045","position":7,"is_corresponding":false},{"id":49576,"name":"Leonard I. Zon","orcid":"0000-0003-0860-926X","position":8,"is_corresponding":false},{"id":648333,"name":"Haley R. Noonan","orcid":"0000-0002-0519-4065","position":0,"is_corresponding":true}],"reference_count":91,"raw_metadata":null,"created_at":"2026-07-19T02:04:37.468651Z","pmid":"38874379","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":[]}