Ceramide synthase 4 overexpression exerts oncogenic properties in breast cancer.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:37885013", "kind": "science-record", "revision": 3, "content_hash": "sha256:b8fa09625a8b3ea1a180e0e878b92037cda88517a59f9fa0292205fd713a9eb1", "created_at": "2026-11-01T19:02:44Z", "updated_at": "2026-11-01T22:10:31Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Ceramide synthase 4 overexpression exerts oncogenic properties in breast cancer.", "doi": "10.1186/s12944-023-01930-z", "pmid": "37885013", "authors": ["Su-Jeong Kim", "Incheol Seo", "Min Hee Kim", "Joo-Won Park", "Shin Kim", "Woo-Jae Park"], "journal": "Lipids in health and disease", "year": 2023, "abstract": "BACKGROUND: Ceramide, a bioactive signaling sphingolipid, has long been implicated in cancer. Members of the ceramide synthase (CerS) family determine the acyl chain lengths of ceramides, with ceramide synthase 4 (CerS4) primarily generating C18-C20-ceramide. Although CerS4 is known to be overexpressed in breast cancer, its role in breast cancer pathogenesis is not well established.\nMETHODS: To investigate the role of CerS4 in breast cancer, public datasets, including The Cancer Genome Atlas (TCGA) and two Gene Expression Omnibus (GEO) datasets (GSE115577 and GSE96058) were analyzed. Furthermore, MCF-7 cells stably overexpressing CerS4 (MCF-7/CerS4) as a model for luminal subtype A (LumA) breast cancer were produced, and doxorubicin (also known as Adriamycin [AD])-resistant MCF-7/ADR cells were generated after prolonged treatment of MCF-7 cells with doxorubicin. Kaplan-Meier survival analysis assessed the clinical significance of CERS4 expression, while Student's t-tests or Analysis of Variance (ANOVA) compared gene expression and cell viability in different MCF-7 cell lines.\nRESULTS: Analysis of the public datasets revealed elevated CERS4 expression in breast cancer, especially in the most common breast cancer subtype, LumA. Persistent CerS4 overexpression in MCF-7 cells activated multiple cancer-associated pathways, including pathways involving sterol regulatory element-binding protein, nuclear factor kappa B (NF-κB), Akt/mammalian target of rapamycin (mTOR), and β-catenin. Furthermore, MCF-7/CerS4 cells acquired doxorubicin, paclitaxel, and tamoxifen resistance, with concomitant upregulation of ATP-binding cassette (ABC) transporter genes, such as ABCB1, ABCC1, ABCC2, ABCC4, and ABCG2. MCF-7/CerS4 cells were characterized by increased cell migration and epithelial-mesenchymal transition (EMT). Finally, CERS4 knockdown in doxorubicin-resistant MCF-7/ADR cells resulted in reduced activation of cancer-associated pathways (NF-κB, Akt/mTOR, β-catenin, and EMT) and diminished chemoresistance, accompanied by ABCB1 and ABCC1 downregulation.\nCONCLUSIONS: Chronic CerS4 overexpression may exert oncogenic effects in breast cancer via alterations in signaling, EMT, and chemoresistance. Therefore, CerS4 may represent an attractive target for anticancer therapy, especially in LumA breast cancer.", "claims": [{"id": "claim-method", "statement": "Kaplan−Meier survival analysis was performed to investigate the relationship between CERS4 expression and overall survival of the patient with LumA breast cancer.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37885013", "locator": "sections[13] \"Analysis of TCGA-BRCA and GEO dataset\" paragraph 2", "quote": "Kaplan−Meier survival analysis was performed to investigate the relationship between CERS4 expression and overall survival of the patient with LumA breast cancer."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37885013", "locator": "sections[28] \"Data Availability\" paragraph 2", "quote": "The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Analysis of the public datasets revealed elevated CERS4 expression in breast cancer, especially in the most common breast cancer subtype, LumA.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:37885013", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Analysis of the public datasets revealed elevated CERS4 expression in breast cancer, especially in the most common breast cancer subtype, LumA."}, {"asset": "source:pmid:37885013", "locator": "sections[16] \"Expression of CERS4 and survival analysis across breast cancer cohorts\" paragraph 2", "quote": "These analyses revealed significantly higher CERS4 mRNA expression levels in tumor tissues than in normal tissues in two cohorts (TCGA-BRCA, P < 0.0001; GSE115577, P < 0.0001; Fig. 1A)."}, {"asset": "source:pmid:37885013", "locator": "sections[16] \"Expression of CERS4 and survival analysis across breast cancer cohorts\" paragraph 2", "quote": "This analysis revealed that higher CERS4 mRNA expression levels were associated with poor overall survival in LumA breast cancer (TCGA-BRCA, P = 0.048; GSE96058, P = 0.0014; Fig. 1C)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "Analysis of the public datasets revealed elevated CERS4 expression in breast cancer, especially in the most common breast cancer subtype, LumA.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:37885013"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "blocked", "blocked_on": "data:accession_absent", "description": "The GEO series accession resolves and its sample accessions are listed. 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Furthermore, MCF-7 cells stably overexpressing CerS4 (MCF-7/Cer", "re, MCF-7 cells stably overexpressing CerS4 (MCF-7/CerS4) as a model for luminal subtype A (Lum", "in (also known as Adriamycin [AD])-resistant MCF-7/ADR cells were generated after prolonged tre", "were generated after prolonged treatment of MCF-7 cells with doxorubicin. Kaplan-Meier surviva"], "order_basis": "paper_text_order:640", "id": "assay:1"}, {"role": "data_generation", "definition_id": "transfection", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.85, "evidence": ["mesenchymal transition (EMT). 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