{"doi":"10.1371/journal.pone.0018128","title":"Lithocholic Acid Is an Eph-ephrin Ligand Interfering with Eph-kinase Activation","abstract":null,"journal":"PLoS ONE","year":2011,"id":629459,"datarank":0.6610078870896381,"base_score":4.406719247264253,"endowment":4.406719247264253,"self_citation_contribution":0.6610078870896381,"citation_network_contribution":0.0,"self_endowment_contribution":0.6610078870896381,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":81,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1630207,"name":"Iftiin Hassan Mohamed","orcid":null,"position":1,"is_corresponding":false},{"id":1630208,"name":"Lisa Flammini","orcid":null,"position":2,"is_corresponding":false},{"id":1630210,"name":"Elisabetta Barocelli","orcid":null,"position":3,"is_corresponding":false},{"id":1630212,"name":"Matteo Incerti","orcid":null,"position":4,"is_corresponding":false},{"id":1630214,"name":"Alessio Lodola","orcid":null,"position":5,"is_corresponding":false},{"id":1630216,"name":"Massimiliano Tognolini","orcid":null,"position":6,"is_corresponding":false},{"id":1630206,"name":"Carmine Giorgio","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Lithocholic Acid Is an Eph-ephrin Ligand Interfering with Eph-kinase Activation","abstract":"Eph-ephrin system plays a central role in a large variety of human cancers. In fact, alterated expression and/or de-regulated function of Eph-ephrin system promotes tumorigenesis and development of a more aggressive and metastatic tumour phenotype. In particular EphA2 upregulation is correlated with tumour stage and progression and the expression of EphA2 in non-transformed cells induces malignant transformation and confers tumorigenic potential. Based on these evidences our aim was to identify small molecules able to modulate EphA2-ephrinA1 activity through an ELISA-based binding screening. We identified lithocholic acid (LCA) as a competitive and reversible ligand inhibiting EphA2-ephrinA1 interaction (Ki = 49 µM). Since each ephrin binds many Eph receptors, also LCA does not discriminate between different Eph-ephrin binding suggesting an interaction with a highly conserved region of Eph receptor family. Structurally related bile acids neither inhibited Eph-ephrin binding nor affected Eph phosphorylation. Conversely, LCA inhibited EphA2 phosphorylation induced by ephrinA1-Fc in PC3 and HT29 human prostate and colon adenocarcinoma cell lines (IC(50) = 48 and 66 µM, respectively) without affecting cell viability or other receptor tyrosine-kinase (EGFR, VEGFR, IGFR1β, IRKβ) activity. LCA did not inhibit the enzymatic kinase activity of EphA2 at 100 µM (LANCE method) confirming to target the Eph-ephrin protein-protein interaction. Finally, LCA inhibited cell rounding and retraction induced by EphA2 activation in PC3 cells. In conclusion, our findings identified a hit compound useful for the development of molecules targeting ephrin system. Moreover, as ephrin signalling is a key player in the intestinal cell renewal, our work could provide an interesting starting point for further investigations about the role of LCA in the intestinal homeostasis.","is_dataset_classified":null,"base_score":4.406719247264253,"endowment":4.406719247264253,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"21479221","pmcid":"PMC3068151","openalex_id":"https://openalex.org/W2086403312","authors":[],"funders":[],"total_grants":0,"fwci":2.8357,"citation_percentile":0.9137692,"influential_citations":0,"citation_trend":[{"year":2012,"count":8},{"year":2013,"count":10},{"year":2014,"count":5},{"year":2015,"count":5},{"year":2016,"count":5},{"year":2017,"count":4},{"year":2018,"count":5},{"year":2019,"count":6},{"year":2020,"count":4},{"year":2021,"count":2},{"year":2022,"count":6},{"year":2023,"count":10},{"year":2024,"count":3},{"year":2025,"count":2},{"year":2026,"count":3}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0018128&type=printable","host_type":"journal"},{"url":"https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0018128&type=printable","host_type":"publisher"},{"url":"http://dx.plos.org/10.1371/journal.pone.0018128","host_type":"publisher"},{"url":"https://doi.org/10.1371/journal.pone.0018128","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/21479221","host_type":"repository"},{"url":"http://citeseerx.ist.psu.edu/viewdoc/summary?doi=10.1.1.349.8720","host_type":""},{"url":"https://doaj.org/article/0b355f8267b24ce7b13039c22bc5a2bf","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/3068151","host_type":"repository"},{"url":"https://figshare.com/articles/Lithocholic_Acid_Is_an_Eph_ephrin_Ligand_Interfering_with_Eph_kinase___Activation/137858","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC3068151","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC3068151?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["Axon Guidance and Neuronal Signaling","Chromatography in Natural Products","Flavonoids in Medical Research","Binding, Competitive","Cell Adhesion","Cell Death","Cell Line, Tumor","Cell Shape","Enzyme Activation","Ephrins","ErbB Receptors","Humans","Ligands","Lithocholic Acid","Phosphorylation","Protein Binding","Receptor, IGF Type 1","Receptors, Eph Family","Receptors, Vascular Endothelial Growth Factor"],"mesh_terms":["Binding, Competitive","Cell Adhesion","Enzyme Activation","Humans","Ligands","Lithocholic Acid","Phosphorylation","Protein Binding","Cell Death","Receptor, IGF Type 1","Receptors, Eph Family","Ephrins","Receptors, Vascular Endothelial Growth Factor","Cell Line, Tumor","Cell Shape","ErbB Receptors"],"keywords":["Erythropoietin-producing hepatocellular (Eph) receptor","Ephrin","EPH receptor A2","Lithocholic acid","Cell biology","Chemistry","Biology","Biochemistry","Cancer research","Receptor tyrosine kinase","Signal transduction","Bile acid"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Peace, Justice and strong institutions"},{"sdg_number":0,"sdg_label":"Reduced inequalities"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-05T18:43:10.495292Z","pmid":null,"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":[]}