{"doi":"10.1016/j.bbadis.2025.168023","title":"Inhibition of ELOVL6 activity impairs mitochondrial respiratory function and inhibits tumor progression in FGFR3-mutated bladder cancer cells","abstract":null,"journal":"Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease","year":2025,"id":593129,"datarank":0.24490193008094913,"base_score":1.6094379124341003,"endowment":1.6094379124341003,"self_citation_contribution":0.24141568686511508,"citation_network_contribution":0.0034862432158340438,"self_endowment_contribution":0.24141568686511508,"citer_contribution":0.0034862432158340438,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":4,"citers_with_citation_signal":1,"citers_with_endowment":1,"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":1518003,"name":"Shiho Hasebe","orcid":null,"position":1,"is_corresponding":false},{"id":1518004,"name":"Takashi Matsuzaka","orcid":null,"position":2,"is_corresponding":false},{"id":1518005,"name":"Akio Hayashi","orcid":null,"position":3,"is_corresponding":false},{"id":1312682,"name":"Hiroshi Ohno","orcid":"0000-0003-2271-4453","position":4,"is_corresponding":false},{"id":1518006,"name":"Kaori Motomura","orcid":null,"position":5,"is_corresponding":false},{"id":1518007,"name":"Shotaro Sakka","orcid":null,"position":6,"is_corresponding":false},{"id":1518008,"name":"Susumu Kohno","orcid":null,"position":7,"is_corresponding":false},{"id":682041,"name":"Hayato Muranaka","orcid":"0000-0003-4835-3836","position":8,"is_corresponding":false},{"id":1410616,"name":"Minako Yamamura","orcid":null,"position":9,"is_corresponding":false},{"id":1440493,"name":"Asuka Suzuki","orcid":"0000-0002-5102-696X","position":10,"is_corresponding":false},{"id":1518009,"name":"Yoshinori Takeuchi","orcid":null,"position":11,"is_corresponding":false},{"id":1518010,"name":"Yoshinori Osaki","orcid":null,"position":12,"is_corresponding":false},{"id":1518011,"name":"Takafumi Miyamoto","orcid":null,"position":13,"is_corresponding":false},{"id":1518013,"name":"Motohiro Sekiya","orcid":null,"position":14,"is_corresponding":false},{"id":1518015,"name":"Hirohito Sone","orcid":null,"position":15,"is_corresponding":false},{"id":1518017,"name":"Naoya Yahagi","orcid":null,"position":16,"is_corresponding":false},{"id":585442,"name":"Yoshimi Nakagawa","orcid":"0000-0001-8710-5232","position":17,"is_corresponding":false},{"id":1518020,"name":"Satoshi Nitta","orcid":null,"position":18,"is_corresponding":false},{"id":1518023,"name":"Shuya Kandori","orcid":null,"position":19,"is_corresponding":false},{"id":1518025,"name":"Takahiro Kojima","orcid":null,"position":20,"is_corresponding":false},{"id":585933,"name":"Chiaki Takahashi","orcid":"0000-0002-8082-8531","position":21,"is_corresponding":false},{"id":617506,"name":"Hiroyuki Nishiyama","orcid":"0000-0001-7423-596X","position":22,"is_corresponding":false},{"id":1278267,"name":"Hitoshi Shimano","orcid":"0000-0002-5562-5572","position":23,"is_corresponding":false},{"id":1518002,"name":"Erika Matsuda","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Inhibition of ELOVL6 activity impairs mitochondrial respiratory function and inhibits tumor progression in FGFR3-mutated bladder cancer cells","abstract":"OBJECTIVE: Increased de novo fatty acid (FA) synthesis is a hallmark of cancer. ELOVL FA elongase 6 (ELOVL6) catalyze chain elongation of C16 saturated and monounsaturated FAs into C18 species and has been implicated in several cancers. This study investigated the role of ELOVL6 in bladder cancer (BC). METHODS: ELOVL6 expression was compared between BC and nontumor tissues. Human BC cell lines with ELOVL6-knockdown were assessed for proliferation and tumor growth. Metabolic and molecular alterations induced by ELOVL6 inhibition were analyzed using lipidomics and transcriptomics. RESULTS: ELOVL6 expression was significantly higher in BC tissues than in controls. In fibroblast growth factor receptor 3 (FGFR3)-mutant BC cell lines, ELOVL6 knockdown suppressed cell growth in vitro and tumor progression in vivo. Lipidomic analysis showed a marked reduction in phosphatidylethanolamine following ELOVL6 knockdown, which was accompanied by lower mitochondrial complex I and II protein levels and impaired mitochondrial oxidative phosphorylation (OXPHOS). RNA sequencing revealed that mitochondrial dysfunction resulting from ELOVL6 knockdown triggered changes in extracellular matrix (ECM) remodeling gene expression and activation of the ECM-integrin-focal adhesion kinase (FAK) pathway, likely as a compensatory response to reduced cell proliferation. CONCLUSION: ELOVL6 regulates lipid composition to preserve mitochondrial function, supporting cell growth and tumorigenesis in FGFR3-mutated BC. Targeting ELOVL6 may represent a novel therapeutic strategy for treating BC, particularly in tumors driven by FGFR3 mutations.","is_dataset_classified":null,"base_score":1.6094379124341003,"endowment":1.6094379124341003,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"40835210","pmcid":null,"openalex_id":"https://openalex.org/W4413275816","authors":[],"funders":[{"funder_name":"Japan Agency for Medical Research and Development","grant_id":"16gm0910003h0002","title":null},{"funder_name":"Japan Agency for Medical Research and Development","grant_id":"22H00474","title":null},{"funder_name":"Japan Agency for Medical Research and Development","grant_id":"20K21643","title":null},{"funder_name":"Japan Agency for Medical Research and Development","grant_id":"24K02851","title":null},{"funder_name":"Cancer Research Institute","grant_id":"","title":null},{"funder_name":"Ministry of Education, Culture, Sports, Science and Technology","grant_id":"","title":null},{"funder_name":"Kanazawa University","grant_id":"","title":null}],"total_grants":7,"fwci":2.3704,"citation_percentile":0.89500256,"influential_citations":0,"citation_trend":[{"year":2026,"count":4}],"oa_status":"hybrid","license":"cc-by","oa_locations":[{"url":"https://doi.org/10.1016/j.bbadis.2025.168023","host_type":"journal"},{"url":"https://doi.org/10.1016/j.bbadis.2025.168023","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S0925443925003710?httpAccept=text/xml","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S0925443925003710?httpAccept=text/plain","host_type":"publisher"},{"url":"https://pubmed.ncbi.nlm.nih.gov/40835210","host_type":"repository"},{"url":"https://kanazawa-u.repo.nii.ac.jp/records/2003883","host_type":"repository"}],"fields_of_study":["Cancer, Lipids, and Metabolism","Fibroblast Growth Factor Research","Fatty Acid Research and Health","Humans","Urinary Bladder Neoplasms","Mitochondria","Cell Line, Tumor","Receptor, Fibroblast Growth Factor, Type 3","Fatty Acid Elongases","Cell Proliferation","Mutation","Animals","Mice","Disease Progression","Female","Male","Gene Expression Regulation, Neoplastic","Oxidative Phosphorylation"],"mesh_terms":["Fatty Acid Elongases","Animals","Urinary Bladder Neoplasms","Female","Humans","Male","Mitochondria","Mutation","Oxidative Phosphorylation","Gene Expression Regulation, Neoplastic","Disease Progression","Cell Line, Tumor","Cell Proliferation","Mice","Receptor, Fibroblast Growth Factor, Type 3"],"keywords":["Cancer research","Biology","Cancer","Function (biology)","Mitochondrion","Internal medicine","Endocrinology","Medicine","Cell biology","Extracellular matrix (ECM)","Fibroblast Growth Factor Receptor 3 (Fgfr3)","Bladder Cancer (Bc)","Elovl Fatty Acid Elongase 6 (Elovl6)","Mitochondrial Oxidative Phosphorylation (Oxphos)"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-26T17:22:51.558871Z","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":[]}