{"doi":"10.1016/j.celrep.2025.116025","title":"IGSF10 is a RET antagonist regulating Ewing sarcoma growth and GnRH neuron migration","abstract":"RET is a receptor tyrosine kinase that plays important roles in development, cancers, and Parkinson's disease. Here, we identify immunoglobulin superfamily member 10 (IGSF10) as a RET antagonist. We show that Ewing sarcoma depends on IGSF10 and that IGSF10 prevents RET-mediated activation of cdc42, a Rho family G protein and a key regulator of Ewing sarcoma growth as well as cell migration. We demonstrate that IGSF10 binds RET and GAS1, a cell surface RET inhibitor, and assembles an inhibitory RET-GAS1 complex, preventing a stimulatory RET-GFRA complex. IGSF10 mutations are associated with delayed puberty, and IGSF10 is shown to be necessary for the proper migration of gonadotropin-releasing hormone (GnRH) neurons. We show that the IGSF10-RET-GAS1-cdc42 pathway regulates migration of GnRH neurons and that IGSF10 mutants linked to delayed puberty are defective in RET-cdc42 regulation. These results reveal a critical role of IGSF10 as a RET antagonist in Ewing sarcoma and GnRH neurons.","journal":"Cell Reports","year":2025,"id":570739,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9496,"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":502090,"name":"Xiuye Ma","orcid":null,"position":1,"is_corresponding":false},{"id":1476648,"name":"Maleeha Akram","orcid":null,"position":2,"is_corresponding":false},{"id":1476649,"name":"Hannah Bow","orcid":null,"position":3,"is_corresponding":false},{"id":1476650,"name":"P. Mandal","orcid":null,"position":4,"is_corresponding":false},{"id":889476,"name":"Naira da Silva Mansano","orcid":"0000-0003-4545-6434","position":5,"is_corresponding":false},{"id":389888,"name":"Yidong Chen","orcid":"0000-0002-3154-6511","position":6,"is_corresponding":false},{"id":432658,"name":"Susan T. Weintraub","orcid":"0000-0002-8328-7814","position":7,"is_corresponding":false},{"id":30173,"name":"Peter J. Houghton","orcid":"0000-0002-2400-8184","position":8,"is_corresponding":false},{"id":395820,"name":"Susan Wray","orcid":"0000-0001-7670-3915","position":9,"is_corresponding":false},{"id":493588,"name":"Yuzuru Shiio","orcid":"0000-0002-3391-9086","position":10,"is_corresponding":false},{"id":502089,"name":"Panneerselvam Jayabal","orcid":null,"position":0,"is_corresponding":true}],"reference_count":69,"raw_metadata":null,"created_at":"2026-07-19T02:57:11.713851Z","pmid":"40700020","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":[]}