{"doi":"10.1016/j.celrep.2024.114445","title":"Pro-survival signaling regulates lipophagy essential for multiple myeloma resistance to stress-induced death","abstract":"Pro-survival metabolic adaptations to stress in tumorigenesis remain less well defined. We find that multiple myeloma (MM) is unexpectedly dependent on beta-oxidation of long-chain fatty acids (FAs) for survival under both basal and stress conditions. However, under stress conditions, a second pro-survival signal is required to sustain FA oxidation (FAO). We previously found that CD28 is expressed on MM cells and transduces a significant pro-survival/chemotherapy resistance signal. We now find that CD28 signaling regulates autophagy/lipophagy that involves activation of the Ca2+→AMPK→ULK1 axis and regulates the translation of ATG5 through HuR, resulting in sustained lipophagy, increased FAO, and enhanced MM survival. Conversely, blocking autophagy/lipophagy sensitizes MM to chemotherapy in vivo. Our findings link a pro-survival signal to FA availability needed to sustain the FAO required for cancer cell survival under stress conditions and identify lipophagy as a therapeutic target to overcome treatment resistance in MM.","journal":"Cell Reports","year":2024,"id":427824,"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":14,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9485,"is_data_producer":false,"deposit_databanks":null,"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":351776,"name":"Colin Chavel","orcid":"0000-0003-1458-8979","position":1,"is_corresponding":false},{"id":351780,"name":"Wensheng Liu","orcid":"0000-0001-9621-2742","position":2,"is_corresponding":false},{"id":729071,"name":"Louise Carlson","orcid":null,"position":3,"is_corresponding":false},{"id":703161,"name":"Sha Cao","orcid":"0000-0003-3033-9219","position":4,"is_corresponding":false},{"id":352483,"name":"Adam Utley","orcid":null,"position":5,"is_corresponding":false},{"id":351782,"name":"Scott H. Olejniczak","orcid":"0000-0001-6857-5554","position":6,"is_corresponding":false},{"id":351783,"name":"Kelvin P. Lee","orcid":"0000-0003-2587-0734","position":7,"is_corresponding":false},{"id":1228551,"name":"Peng Peng","orcid":"0000-0003-4226-6248","position":0,"is_corresponding":true}],"reference_count":82,"raw_metadata":null,"created_at":"2026-07-19T01:58:52.576447Z","pmid":"38968073","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":[]}