{"doi":"10.1101/2025.07.17.665258","title":"Lean breast adipocytes secrete an oxylipin that suppresses breast cancer via ferroptosis","abstract":"Obesity is predicted to become the largest modifiable risk factor for breast cancer in postmenopausal women, yet the mechanisms underlying this association are unclear. We identified a novel role for the endogenous oxylipin 9S-HODE, secreted by lean adipocytes, to induce ferroptosis in breast cancer cells while sparing normal breast epithelial cells. Obese adipocytes fail to secrete 9S-HODE, suggesting that the loss of ferroptosis induction significantly contributes to the acceleration of obesity-associated breast cancer. Consequently, the inhibition of ferroptosis accelerates breast cancer in lean, but not obese, mice. Further, 9S-HODE inhibits the growth of patient-derived breast cancer organoids, and supplementing 9S-HODE into tumors in obese mice is sufficient to reduce tumor burden, underscoring its potential as a therapeutic agent.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":570672,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9467,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1233161,"name":"Abigail E. Jackson","orcid":"0009-0004-9842-5695","position":1,"is_corresponding":false},{"id":1217724,"name":"Elisabeth A. Brown","orcid":null,"position":2,"is_corresponding":false},{"id":251369,"name":"J. Alan Maschek","orcid":"0000-0003-3217-2299","position":3,"is_corresponding":false},{"id":587947,"name":"David H. Lum","orcid":"0000-0002-0159-8724","position":4,"is_corresponding":false},{"id":232411,"name":"James E. Cox","orcid":"0000-0002-5977-2350","position":5,"is_corresponding":false},{"id":30200,"name":"Alana L. Welm","orcid":"0000-0002-1412-1351","position":6,"is_corresponding":false},{"id":560697,"name":"Keren I. Hilgendorf","orcid":"0000-0001-8377-8384","position":7,"is_corresponding":false},{"id":1243008,"name":"Meghan C. Curtin","orcid":null,"position":0,"is_corresponding":true}],"reference_count":60,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:57:11.713851Z","pmid":"40777459","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":[]}