{"doi":"10.1371/journal.pone.0305490","title":"Cadherin-11 contributes to the heterogenous and dynamic Wnt-Wnt-β-catenin pathway activation in Ewing sarcoma","abstract":"Ewing sarcoma is the second most common bone cancer in children, and while patients who present with metastatic disease at the time of diagnosis have a dismal prognosis. Ewing sarcoma tumors are driven by the fusion gene EWS/Fli1, and while these tumors are genetically homogenous, the transcriptional heterogeneity can lead to a variety of cellular processes including metastasis. In this study, we demonstrate that in Ewing sarcoma cells, the canonical Wnt/β-Catenin signaling pathway is heterogeneously activated in vitro and in vivo, correlating with hypoxia and EWS/Fli1 activity. Ewing sarcoma cells predominantly express β-Catenin on the cell membrane bound to CDH11, which can respond to exogenous Wnt ligands leading to the immediate activation of Wnt/β-Catenin signaling within a tumor. Knockdown of CDH11 leads to delayed and decreased response to exogenous Wnt ligand stimulation, and ultimately decreased metastatic propensity. Our findings strongly indicate that CDH11 is a key component of regulating Wnt//β-Catenin signaling heterogeneity within Ewing sarcoma tumors, and is a promising molecular target to alter Wnt//β-Catenin signaling in Ewing sarcoma patients.","journal":"PLoS ONE","year":2024,"id":475849,"datarank":0.20794415416798362,"base_score":1.3862943611198906,"endowment":1.3862943611198906,"self_citation_contribution":0.20794415416798362,"citation_network_contribution":0.0,"self_endowment_contribution":0.20794415416798362,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":2,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9498,"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":1313165,"name":"Tyler Biebighauser","orcid":null,"position":1,"is_corresponding":false},{"id":521237,"name":"Deandra Walker","orcid":null,"position":2,"is_corresponding":false},{"id":1313166,"name":"Jillian Oviedo","orcid":null,"position":3,"is_corresponding":false},{"id":1312776,"name":"Sarah Nelson-Taylor","orcid":"0009-0003-7664-4400","position":4,"is_corresponding":false},{"id":760548,"name":"Avery Bodlak","orcid":"0000-0001-9207-1532","position":5,"is_corresponding":false},{"id":1265971,"name":"Timothy Porfilio","orcid":"0000-0003-3699-9963","position":6,"is_corresponding":false},{"id":1312777,"name":"Naoki Oike","orcid":"0000-0003-3067-392X","position":7,"is_corresponding":false},{"id":10973,"name":"Andrew Goodspeed","orcid":"0000-0001-7055-7128","position":8,"is_corresponding":false},{"id":329711,"name":"Masanori Hayashi","orcid":"0000-0002-9508-0159","position":9,"is_corresponding":false},{"id":952394,"name":"Ryota Shirai","orcid":"0000-0002-1015-3444","position":0,"is_corresponding":true}],"reference_count":49,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:06:21.071690Z","pmid":"38875295","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":[]}