{"doi":"10.1101/2022.09.23.509253","title":"Reprogramming of Iron Metabolism Confers Ferroptosis Resistance in ECM-Detached Cells","abstract":"Summary Cancer cells often acquire resistance to cell death programs induced by loss of integrin-mediated attachment to extracellular matrix (ECM). Given that adaptation to ECM-detached conditions can facilitate tumor progression and metastasis, there is significant interest in effective elimination of ECM-detached cancer cells. Here, we find that ECM-detached cells are remarkably resistant to the induction of ferroptosis. While alterations in membrane lipid content are observed during ECM-detachment, it is instead fundamental changes in iron metabolism that underlie resistance of ECM-detached cells to ferroptosis. More specifically, our data demonstrate that levels of free iron are low during ECM-detachment due to changes in both iron uptake and iron storage. In addition, we establish that lowering the levels of iron storage proteins sensitizes ECM-detached cells to death by ferroptosis. Taken together, our data suggest that therapeutics designed to kill cancer cells by ferroptosis may be hindered by lack of efficacy towards ECM-detached cells.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":301909,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9493,"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":993892,"name":"Abigail M. Abikoye","orcid":null,"position":1,"is_corresponding":false},{"id":993893,"name":"Brett P. McLaughlin","orcid":null,"position":2,"is_corresponding":false},{"id":993894,"name":"Ryan S. Middleton","orcid":null,"position":3,"is_corresponding":false},{"id":503196,"name":"Ryan D. Sheldon","orcid":"0000-0002-1573-9719","position":4,"is_corresponding":false},{"id":232805,"name":"Russell G. Jones","orcid":"0000-0003-2250-4675","position":5,"is_corresponding":false},{"id":993391,"name":"Zachary T. Schafer","orcid":"0000-0001-9227-3118","position":6,"is_corresponding":false},{"id":242716,"name":"Jianping He","orcid":"0009-0001-6177-4179","position":0,"is_corresponding":true}],"reference_count":57,"raw_metadata":null,"created_at":"2026-07-19T00:32:06.309890Z","pmid":null,"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":[]}