{"doi":"10.1016/j.celrep.2024.115130","title":"SLC7A5 is required for cancer cell growth under arginine-limited conditions","abstract":"Tumor cells must optimize metabolite acquisition between synthesis and uptake from a microenvironment characterized by hypoxia, lactate accumulation, and depletion of many amino acids, including arginine. We performed a metabolism-focused functional screen using CRISPR-Cas9 to identify pathways and factors that enable tumor growth in an arginine-depleted environment. Our screen identified the SLC-family transporter SLC7A5 as required for growth, and we hypothesized that this protein functions as a high-affinity citrulline transporter. Using isotope tracing experiments, we show that citrulline uptake and metabolism into arginine are dependent upon expression of SLC7A5. Pharmacological inhibition of SLC7A5 blocks growth under low-arginine conditions across a diverse group of cancer cell lines. Loss of SLC7A5 reduces tumor growth and citrulline import in a mouse tumor model. We identify a conditionally essential role for SLC7A5 in arginine metabolism, and we propose that SLC7A5-targeting therapeutic strategies in cancer may be effective in the context of arginine limitation.","journal":"Cell Reports","year":2025,"id":515642,"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":12,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9563,"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":1349648,"name":"Austin Bender","orcid":null,"position":1,"is_corresponding":false},{"id":1349649,"name":"Alexis Bowles","orcid":null,"position":2,"is_corresponding":false},{"id":232407,"name":"Alex J. Bott","orcid":"0000-0003-2273-8922","position":3,"is_corresponding":false},{"id":1379975,"name":"Joshua Tay","orcid":"0000-0002-0851-0537","position":4,"is_corresponding":false},{"id":791092,"name":"Allie H. Grossmann","orcid":"0000-0002-7665-1403","position":5,"is_corresponding":false},{"id":232415,"name":"Jared Rutter","orcid":"0000-0002-2710-9765","position":6,"is_corresponding":false},{"id":232412,"name":"Gregory S. Ducker","orcid":"0000-0002-8651-6846","position":7,"is_corresponding":false},{"id":562241,"name":"Kyle Dunlap","orcid":"0000-0002-3239-6439","position":0,"is_corresponding":true}],"reference_count":85,"raw_metadata":null,"created_at":"2026-07-19T02:48:39.436300Z","pmid":"39756034","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":[]}