Bulk and single-cell transcriptome profiling reveal extracellular matrix mechanical regulation of lipid metabolism reprograming through YAP/TEAD4/ACADL axis in hepatocellular carcinoma.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:37151879", "kind": "science-record", "revision": 4, "content_hash": "sha256:5002a414bbd28d6ec986307808c02a2e11488e4854fddd1014be82003eb2d961", "created_at": "2026-11-01T19:01:48Z", "updated_at": "2026-11-01T22:51:50Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Bulk and single-cell transcriptome profiling reveal extracellular matrix mechanical regulation of lipid metabolism reprograming through YAP/TEAD4/ACADL axis in hepatocellular carcinoma.", "doi": "10.7150/ijbs.82177", "pmid": "37151879", "authors": ["Jingwei Cai", "Tianyi Chen", "Zhiyu Jiang", "Jiafei Yan", "Zhengtao Ye", "Yeling Ruan", "Liye Tao", "Zefeng Shen", "Xiao Liang", "Yifan Wang", "Junjie Xu", "Xiujun Cai"], "journal": "International journal of biological sciences", "year": 2023, "abstract": "Emerging studies have revealed matrix stiffness promotes hepatocellular carcinoma (HCC) development. We studied metabolic dysregulation in HCC using the TCGA-LIHC database (n=374) and GEO datasets (GSE14520). HCC samples were classified into three heterogeneous metabolic pathway subtypes with different metabolic profiles: Cluster 1, an ECM-producing subtype with upregulated glycan metabolism; Cluster 2, a hybrid subtype with partial pathway dysregulation. Cluster 3, a lipogenic subtype with upregulated lipid metabolism; These three subtypes have different prognosis, clinical features and genomic alterations. We identified key enzymes that respond to matrix stiffness and regulate lipid metabolism through bioinformatic analysis. We found long-chain acyl-CoA dehydrogenase (ACADL) is a mechanoreactive enzyme that reprograms HCC cell lipid metabolism in response to extracellular matrix stiffness. ACADL is also regarded as tumor suppressor in HCC. We found that increased extracellular matrix stiffness led to activation of Yes-associated protein (YAP) and the YAP/TEA Domain transcription factor 4 (TEAD4) transcriptional complex was able to directly repress ACADL at the transcriptional level. The ACADL-dependent mechanoresponsive pathway is a potential therapeutic target for HCC treatment.", "claims": [{"id": "claim-method", "statement": "The Student t test was used for comparison between 2 groups. One-way analysis of variance (ANOVA) was used for comparisons among 3 or more groups.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37151879", "locator": "sections[28] \"Statistical analysis\" paragraph 2", "quote": "The Student t test was used for comparison between 2 groups. One-way analysis of variance (ANOVA) was used for comparisons among 3 or more groups."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Source data used are available from the corresponding author upon reasonable request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37151879", "locator": "sections[30] \"ack\" paragraph 1", "quote": "Source data used are available from the corresponding author upon reasonable request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Long-chain acyl-CoA dehydrogenase (ACADL) is a mechanoreactive enzyme that reprograms HCC cell lipid metabolism in response to extracellular matrix stiffness.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:37151879", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "We found long-chain acyl-CoA dehydrogenase (ACADL) is a mechanoreactive enzyme that reprograms HCC cell lipid metabolism in response to extracellular matrix stiffness."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "Long-chain acyl-CoA dehydrogenase (ACADL) is a mechanoreactive enzyme that reprograms HCC cell lipid metabolism in response to extracellular matrix stiffness.", "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:37151879"], "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": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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