{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T17:12:09Z","timestamp":1781284329618,"version":"3.54.1"},"reference-count":33,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2023,3,8]],"date-time":"2023-03-08T00:00:00Z","timestamp":1678233600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["431984000"],"award-info":[{"award-number":["431984000"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["310030_189102\/1"],"award-info":[{"award-number":["310030_189102\/1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["804474"],"award-info":[{"award-number":["804474"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"publisher","award":["431984000"],"award-info":[{"award-number":["431984000"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"publisher","award":["310030_189102\/1"],"award-info":[{"award-number":["310030_189102\/1"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"publisher","award":["804474"],"award-info":[{"award-number":["804474"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"name":"European Union\u2019s Horizon 2020 research and innovation programme","award":["431984000"],"award-info":[{"award-number":["431984000"]}]},{"name":"European Union\u2019s Horizon 2020 research and innovation programme","award":["310030_189102\/1"],"award-info":[{"award-number":["310030_189102\/1"]}]},{"name":"European Union\u2019s Horizon 2020 research and innovation programme","award":["804474"],"award-info":[{"award-number":["804474"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Clear cell renal cell carcinoma (ccRCC) is the most common histological subtype of renal cancer, and inactivation of the VHL tumor suppressor gene is found in almost all cases of hereditary and sporadic ccRCCs. CcRCC is associated with the reprogramming of fatty acid metabolism, and stearoyl-CoA desaturases (SCDs) are the main enzymes controlling fatty acid composition in cells. In this study, we report that mRNA and protein expression of the stearoyl-CoA desaturase SCD5 is downregulated in VHL-deficient cell lines. Similarly, in C. elegans\u00a0vhl-1 mutants, FAT-7\/SCD5 activity is repressed, supporting an evolutionary conservation. SCD5 regulation by VHL depends on HIF, and loss of SCD5 promotes cell proliferation and a metabolic shift towards ceramide production. In summary, we identify a novel regulatory function of VHL in relation to SCD5 and fatty acid metabolism, and propose a new mechanism of how loss of VHL may contribute to ccRCC tumor formation and progression.<\/jats:p>","DOI":"10.3390\/cells12060835","type":"journal-article","created":{"date-parts":[[2023,3,8]],"date-time":"2023-03-08T03:59:32Z","timestamp":1678247972000},"page":"835","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["SCD5 Regulation by VHL Affects Cell Proliferation and Lipid Homeostasis in ccRCC"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6455-5641","authenticated-orcid":false,"given":"Athina","family":"Ganner","sequence":"first","affiliation":[{"name":"Renal Division, Department of Medicine, Medical Center\u2014University of Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonia","family":"Philipp","sequence":"additional","affiliation":[{"name":"Renal Division, Department of Medicine, Medical Center\u2014University of Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5245-1781","authenticated-orcid":false,"given":"Simon","family":"Lagies","sequence":"additional","affiliation":[{"name":"Core Competence Metabolomics, Hilde-Mangold-Haus, University of Freiburg, 79104 Freiburg, Germany"},{"name":"Institute of Organic Chemistry, University of Freiburg, 79104 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Wingendorf","sequence":"additional","affiliation":[{"name":"Renal Division, Department of Medicine, Medical Center\u2014University of Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Wang","sequence":"additional","affiliation":[{"name":"Renal Division, Department of Medicine, Medical Center\u2014University of Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felicitas","family":"Pilz","sequence":"additional","affiliation":[{"name":"Renal Division, Department of Medicine, Medical Center\u2014University of Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Welte","sequence":"additional","affiliation":[{"name":"Renal Division, Department of Medicine, Medical Center\u2014University of Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelli","family":"Grand","sequence":"additional","affiliation":[{"name":"Institute of Anatomy, Faculty of Medicine, University of Zurich, 8057 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soeren S.","family":"Lienkamp","sequence":"additional","affiliation":[{"name":"Institute of Anatomy, Faculty of Medicine, University of Zurich, 8057 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marinella","family":"Klein","sequence":"additional","affiliation":[{"name":"Renal Division, Department of Medicine, Medical Center\u2014University of Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernd","family":"Kammerer","sequence":"additional","affiliation":[{"name":"Core Competence Metabolomics, Hilde-Mangold-Haus, University of Freiburg, 79104 Freiburg, Germany"},{"name":"Institute of Organic Chemistry, University of Freiburg, 79104 Freiburg, Germany"},{"name":"BIOSS, Centre for Biological Signalling Studies, University of Freiburg, 79104 Freiburg, Germany"},{"name":"Spemann Graduate School of Biology and Medicine (SGBM), University of Freiburg, 79104 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2735-5509","authenticated-orcid":false,"given":"Ian J.","family":"Frew","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I, Medical Center\u2014University of Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerd","family":"Walz","sequence":"additional","affiliation":[{"name":"Renal Division, Department of Medicine, Medical Center\u2014University of Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, 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