{"doi":"10.1101/2023.12.20.572603","title":"Galectin-3-binding protein inhibits extracellular heparan 6- <i>O</i> -endosulfatse Sulf-2","abstract":"Abstract Human extracellular 6- O -endosulfatases Sulf-1 and Sulf-2 are the only enzymes that post-synthetically alter the 6- O sulfation of heparan sulfate proteoglycans (HSPG), which regulates interactions of HSPG with many proteins. Oncogenicity of Sulf-2 in different cancers has been documented and we have shown that Sulf-2 is associated with poor survival outcomes in head and neck squamous cell carcinoma (HNSCC). In spite of its importance, limited information is available on direct protein-protein interactions of the Sulf-2 protein in the tumor microenvironment. In this study, we used monoclonal antibody (mAb) affinity purification and mass spectrometry to identify galectin-3-binding protein (LG3BP) as a highly specific binding partner of Sulf-2 in the secretome of HNSCC cell lines. We validated their direct interaction in vitro using recombinant proteins and have shown that the chondroitin sulfate (CS) covalently bound to the Sulf-2 influences the binding to LG3BP. We confirmed importance of the CS chain for the interaction by generating a mutant Sulf-2 protein that lacks the CS. Importantly, we have shown that the LG3BP inhibits Sulf-2 activity in vitro in a concentration dependent manner. As a consequence, the addition of LG3BP to a spheroid cell culture inhibited invasion of the HNSCC cells into Matrigel. Thus, Sulf-2 interaction with LG3BP has functional relevance, and may regulate physiological activity of the Sulf-2 enzyme as well as its activity in the tumor microenvironment.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":415274,"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":0.9533,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":325659,"name":"Július Benický","orcid":"0000-0002-1941-1622","position":1,"is_corresponding":false},{"id":1109142,"name":"Reem Aljuhani","orcid":"0009-0000-1466-1238","position":2,"is_corresponding":false},{"id":1109141,"name":"Pritha Mukherjee","orcid":"0000-0001-6573-4580","position":3,"is_corresponding":false},{"id":315105,"name":"Zora Nováková","orcid":"0000-0001-9804-6346","position":4,"is_corresponding":false},{"id":315109,"name":"Cyril Bařinka","orcid":"0000-0003-2751-3060","position":5,"is_corresponding":false},{"id":325663,"name":"Radoslav Goldman","orcid":"0000-0003-1304-0522","position":6,"is_corresponding":false},{"id":979201,"name":"Aswini Panigrahi","orcid":"0009-0006-3111-9030","position":0,"is_corresponding":true}],"reference_count":41,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:22:12.933438Z","pmid":"38187586","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":[]}