{"doi":"10.1016/j.celrep.2022.110796","title":"Lipogenesis mediated by OGR1 regulates metabolic adaptation to acid stress in cancer cells via autophagy","abstract":"Malignant tumors exhibit altered metabolism resulting in a highly acidic extracellular microenvironment. Here, we show that cytoplasmic lipid droplet (LD) accumulation, indicative of a lipogenic phenotype, is a cellular adaption to extracellular acidity. LD marker PLIN2 is strongly associated with poor overall survival in breast cancer patients. Acid-induced LD accumulation is triggered by activation of the acid-sensing G-protein-coupled receptor (GPCR) OGR1, which is expressed highly in breast tumors. OGR1 depletion inhibits acid-induced lipid accumulation, while activation by a synthetic agonist triggers LD formation. Inhibition of OGR1 downstream signaling abrogates the lipogenic phenotype, which can be rescued with OGR1 ectopic expression. OGR1-depleted cells show growth inhibition under acidic growth conditions in vitro and tumor formation in vivo. Isotope tracing shows that the source of lipid precursors is primarily autophagy-derived ketogenic amino acids. OGR1-depleted cells are defective in endoplasmic reticulum stress response and autophagy and hence fail to accumulate LDs affecting survival under acidic stress.","journal":"Cell Reports","year":2022,"id":239747,"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":48,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9571,"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":313914,"name":"Iqbal Mahmud","orcid":"0000-0001-7729-8122","position":1,"is_corresponding":false},{"id":317135,"name":"Rohit Mahar","orcid":"0000-0002-9801-4173","position":2,"is_corresponding":false},{"id":866768,"name":"Crystal Griffith","orcid":null,"position":3,"is_corresponding":false},{"id":866032,"name":"Michael Langsen","orcid":"0000-0002-1145-3262","position":4,"is_corresponding":false},{"id":663574,"name":"Jonathan V. Nguyen","orcid":"0000-0001-6146-2047","position":5,"is_corresponding":false},{"id":822127,"name":"Jonathan W. Wojtkowiak","orcid":null,"position":6,"is_corresponding":false},{"id":256178,"name":"Pawel Swietach","orcid":"0000-0002-9945-9473","position":7,"is_corresponding":false},{"id":255974,"name":"Robert A. Gatenby","orcid":"0000-0002-1621-1510","position":8,"is_corresponding":false},{"id":576286,"name":"Marilyn M. Bui","orcid":"0000-0003-4963-2255","position":9,"is_corresponding":false},{"id":317136,"name":"Matthew E. Merritt","orcid":"0000-0003-4617-9651","position":10,"is_corresponding":false},{"id":866769,"name":"Patricia McDonald","orcid":null,"position":11,"is_corresponding":false},{"id":294955,"name":"Timothy J. Garrett","orcid":"0000-0003-1623-009X","position":12,"is_corresponding":false},{"id":65782,"name":"Robert J. Gillies","orcid":"0000-0002-8888-7747","position":13,"is_corresponding":false},{"id":256177,"name":"Smitha Pillai","orcid":"0000-0001-9718-5010","position":0,"is_corresponding":true}],"reference_count":65,"raw_metadata":null,"created_at":"2026-07-19T00:22:41.699779Z","pmid":"35545051","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":[]}