{"doi":"10.1073/pnas.2315925121","title":"CD73 contributes to the pathogenesis of fusion-negative rhabdomyosarcoma through the purinergic signaling pathway","abstract":"Rhabdomyosarcoma (RMS) is the most common type of soft tissue sarcoma in children and adolescents. Fusion-negative RMS (FN-RMS) accounts for more than 80% of all RMS cases. The long-term event-free survival rate for patients with high-grade FN-RMS is below 30%, highlighting the need for improved therapeutic strategies. CD73 is a 5′ ectonucleotidase that hydrolyzes AMP to adenosine and regulates the purinergic signaling pathway. We found that CD73 is elevated in FN-RMS tumors that express high levels of TWIST2. While high expression of CD73 contributes to the pathogenesis of multiple cancers, its role in FN-RMS has not been investigated. We found that CD73 knockdown decreased FN-RMS cell growth while up-regulating the myogenic differentiation program. Moreover, mutation of the catalytic residues of CD73 rendered the protein enzymatically inactive and abolished its ability to stimulate FN-RMS growth. Overexpression of wildtype CD73, but not the catalytically inactive mutant, in CD73 knockdown FN-RMS cells restored their growth capacity. Likewise, treatment with an adenosine receptor A 2A-B agonist partially rescued FN-RMS cell proliferation and bypassed the CD73 knockdown defective growth phenotype. These results demonstrate that the catalytic activity of CD73 contributes to the pathogenic growth of FN-RMS through the activation of the purinergic signaling pathway. Therefore, targeting CD73 and the purinergic signaling pathway represents a potential therapeutic approach for FN-RMS patients.","journal":"Proceedings of the National Academy of Sciences","year":2024,"id":437655,"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":10,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9495,"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":251125,"name":"Akansha M. Shah","orcid":"0000-0001-6902-106X","position":1,"is_corresponding":false},{"id":362002,"name":"Víctor López","orcid":"0000-0003-1618-5786","position":2,"is_corresponding":false},{"id":362003,"name":"Vincent S. Tagliabracci","orcid":"0000-0002-9735-4678","position":3,"is_corresponding":false},{"id":251163,"name":"Kenian Chen","orcid":"0000-0002-4083-841X","position":4,"is_corresponding":false},{"id":251167,"name":"Lin Xu","orcid":"0000-0001-5815-4457","position":5,"is_corresponding":false},{"id":251128,"name":"Rhonda Bassel‐Duby","orcid":"0000-0001-7568-410X","position":6,"is_corresponding":false},{"id":225271,"name":"Eric N. Olson","orcid":"0000-0003-1151-8262","position":7,"is_corresponding":false},{"id":251127,"name":"Ning Liu","orcid":"0000-0003-0257-1889","position":8,"is_corresponding":false},{"id":1233210,"name":"Karla Cano Hernandez","orcid":"0000-0002-6810-141X","position":0,"is_corresponding":true}],"reference_count":33,"raw_metadata":null,"created_at":"2026-07-19T02:00:34.490087Z","pmid":"38227654","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":[]}