{"doi":"10.3390/biom10071035","title":"Galectin-3 Stimulates Tyro3 Receptor Tyrosine Kinase and Erk Signalling, Cell Survival and Migration in Human Cancer Cells","abstract":"<jats:p>The TAM (Tyro3, Axl, MerTK) subfamily of receptor tyrosine kinases (RTKs) and their ligands, Gas6 and protein S (ProS1), are implicated in tumorigenesis and chemoresistance in various cancers. The β-galactoside binding protein galectin-3 (Gal-3), which is also implicated in oncogenesis, has previously been shown to be a ligand for MerTK. However, the selectivity of Gal-3 for the other TAM receptors, and its TAM-mediated signalling and functional properties in cancer cells, remain to be explored. The present study was aimed at determining these, including through direct comparison of Gal-3 with the two canonical TAM ligands. Exogenous Gal-3 rapidly stimulated Tyro3 receptor phosphorylation to the same extent as the Tyro3 ligand ProS1, but not Axl, in the cultured human cancer cell lines SCC-25 (express both Tyro3 and Axl) and MGH-U3 (express Tyro3 only). Gal-3 also activated intracellular Erk and Akt kinases in both cell lines and furthermore protected cells from acute apoptosis induced by staurosporine but not from serum-starvation induced apoptosis. In addition, Gal-3 significantly stimulated cancer cell migration rate in the presence of the Axl blocker BGB324. Therefore, these results have shown Gal-3 to be a novel agonist for Tyro3 RTK, activating a Tyro3-Erk signalling axis, as well as Akt signalling, in cancer cells that promotes cell survival, cell cycle progression and cell migration. These data therefore reveal a novel mechanism of Tyro3 RTK activation through the action of Gal-3 that contrasts with those of the known TAM ligands Gas6 and ProS1.</jats:p>","journal":"Biomolecules","year":2020,"id":602701,"datarank":0.47670807455219194,"base_score":3.1780538303479458,"endowment":3.1780538303479458,"self_citation_contribution":0.47670807455219194,"citation_network_contribution":0.0,"self_endowment_contribution":0.47670807455219194,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":23,"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":1545848,"name":"Sassan Hafizi","orcid":"0000-0002-4539-0888","position":1,"is_corresponding":false},{"id":1545846,"name":"Nour Al Kafri","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Galectin-3 Stimulates Tyro3 Receptor Tyrosine Kinase and Erk Signalling, Cell Survival and Migration in Human Cancer Cells","abstract":"<jats:p>The TAM (Tyro3, Axl, MerTK) subfamily of receptor tyrosine kinases (RTKs) and their ligands, Gas6 and protein S (ProS1), are implicated in tumorigenesis and chemoresistance in various cancers. The β-galactoside binding protein galectin-3 (Gal-3), which is also implicated in oncogenesis, has previously been shown to be a ligand for MerTK. However, the selectivity of Gal-3 for the other TAM receptors, and its TAM-mediated signalling and functional properties in cancer cells, remain to be explored. The present study was aimed at determining these, including through direct comparison of Gal-3 with the two canonical TAM ligands. Exogenous Gal-3 rapidly stimulated Tyro3 receptor phosphorylation to the same extent as the Tyro3 ligand ProS1, but not Axl, in the cultured human cancer cell lines SCC-25 (express both Tyro3 and Axl) and MGH-U3 (express Tyro3 only). Gal-3 also activated intracellular Erk and Akt kinases in both cell lines and furthermore protected cells from acute apoptosis induced by staurosporine but not from serum-starvation induced apoptosis. In addition, Gal-3 significantly stimulated cancer cell migration rate in the presence of the Axl blocker BGB324. Therefore, these results have shown Gal-3 to be a novel agonist for Tyro3 RTK, activating a Tyro3-Erk signalling axis, as well as Akt signalling, in cancer cells that promotes cell survival, cell cycle progression and cell migration. These data therefore reveal a novel mechanism of Tyro3 RTK activation through the action of Gal-3 that contrasts with those of the known TAM ligands Gas6 and ProS1.</jats:p>","is_dataset_classified":null,"base_score":3.1780538303479458,"endowment":3.1780538303479458,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"32664510","pmcid":"PMC7407973","openalex_id":"https://openalex.org/W3041728042","authors":[],"funders":[],"total_grants":0,"fwci":1.2173,"citation_percentile":0.78946346,"influential_citations":0,"citation_trend":[{"year":2021,"count":10},{"year":2022,"count":4},{"year":2023,"count":3},{"year":2024,"count":2},{"year":2025,"count":2},{"year":2026,"count":2}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://www.mdpi.com/2218-273X/10/7/1035/pdf?version=1594455481","host_type":"journal"},{"url":"https://www.mdpi.com/2218-273X/10/7/1035/pdf?version=1594455481","host_type":"publisher"},{"url":"https://www.mdpi.com/2218-273X/10/7/1035/pdf","host_type":"publisher"},{"url":"https://doi.org/10.3390/biom10071035","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/32664510","host_type":"repository"},{"url":"https://www.mdpi.com/2218-273X/10/7/1035","host_type":"repository"},{"url":"https://doaj.org/article/482ca277a5194757b2407a8b97174707","host_type":"repository"},{"url":"http://doi.org/10.3390/biom10071035","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/7407973","host_type":"repository"},{"url":"https://researchportal.port.ac.uk/portal/en/publications/galectin3-stimulates-tyro3-receptor-tyrosine-kinase-and-erk-signalling-cell-survival-and-migration-in-human-cancer-cells(8391ea66-fcfb-466f-be15-364c9960c2e9).html","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC7407973","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC7407973?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["Phagocytosis and Immune Regulation","Erythrocyte Function and Pathophysiology","Benzocycloheptenes","Blood Proteins","Cell Line, Tumor","Cell Movement","Cell Survival","Galectin 3","Galectins","Gene Expression Regulation, Neoplastic","Humans","MAP Kinase Signaling System","Neoplasms","Phosphorylation","Protein S","Proto-Oncogene Proteins","Receptor Protein-Tyrosine Kinases","Staurosporine","Triazoles","Axl Receptor Tyrosine Kinase"],"mesh_terms":["Axl Receptor Tyrosine Kinase","Benzocycloheptenes","Blood Proteins","Cell Movement","Cell Survival","Humans","Neoplasms","Phosphorylation","Proto-Oncogene Proteins","Triazoles","Gene Expression Regulation, Neoplastic","Protein S","Staurosporine","Receptor Protein-Tyrosine Kinases","MAP Kinase Signaling System","Galectins","Galectin 3","Cell Line, Tumor"],"keywords":["GAS6","MERTK","Receptor tyrosine kinase","Efferocytosis","Cancer research","Protein kinase B","Cell biology","Cancer cell","Biology","Tyrosine kinase","Receptor Protein-Tyrosine Kinases","MAPK/ERK pathway","Carcinogenesis","Signal transduction","Chemistry","Cancer","Biochemistry","Macrophage","Ligand","Protein S","galectin-3","Axl","Tyro3"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"doi"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-29T20:04:11.085508Z","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":[]}