Marthe-Susanna Wegner, Nina Schömel, Ellen M. Olzomer, Sandra Trautmann, Catherine Olesch, Frances L. Byrne, Bernhard Brüne, Robert Gurke, Nerea Ferreirós Bouzas, Andreas Weigert, Gerd Geisslinger, Kyle L. Hoehn
- Hepatocellular carcinoma (HCC) is one of the most difficult cancer types to treat. Liver cancer is often diagnosed at late stages and therapeutic treatment is frequently accompanied by development of multidrug resistance. This leads to poor outcomes for cancer patients. Understanding the fundamental molecular mechanisms leading to liver cancer development is crucial for developing new therapeutic approaches, which are more efficient in treating cancer. Mice with a liver specific UDP-glucose ceramide glucosyltransferase (UGCG) knockout (KO) show delayed diethylnitrosamine (DEN)-induced liver tumor growth. Accordingly, the rationale for our study was to determine whether UGCG overexpression is sufficient to drive cancer phenotypes in liver cells. We investigated the effect of UGCG overexpression (OE) on normal murine liver (NMuLi) cells. Increased UGCG expression results in decreased mitochondrial respiration and glycolysis, which is reversible by treatment with EtDO-P4, an UGCG inhibitor. Furthermore, tumor markers such as FGF21 and EPCAM are lowered following UGCG OE, which could be related to glucosylceramide (GlcCer) and lactosylceramide (LacCer) accumulation in glycosphingolipid-enriched microdomains (GEMs) and subsequently altered signaling protein phosphorylation. These cellular processes lead to decreased proliferation in NMuLi/UGCG OE cells. Our data show that increased UGCG expression itself does not induce pro-cancerous processes in normal liver cells, which indicates that increased GlcCer expression leads to different outcomes in different cancer types.
MetadatenAuthor: | Marthe-Susanna WegnerORCiDGND, Nina SchömelGND, Ellen M. Olzomer, Sandra TrautmannGND, Catherine OleschORCiDGND, Frances L. ByrneORCiD, Bernhard BrüneORCiD, Robert GurkeORCiDGND, Nerea Ferreirós BouzasORCiDGND, Andreas WeigertORCiDGND, Gerd GeisslingerORCiDGND, Kyle L. HoehnORCiD |
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URN: | urn:nbn:de:hebis:30:3-695668 |
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DOI: | https://doi.org/10.1007/s00018-021-03958-9 |
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ISSN: | 1420-9071 |
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Parent Title (English): | Cellular and molecular life sciences |
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Publisher: | Springer International Publishing AG |
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Place of publication: | Cham (ZG) |
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Document Type: | Article |
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Language: | English |
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Date of Publication (online): | 2021/10/09 |
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Date of first Publication: | 2021/10/09 |
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Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
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Release Date: | 2023/09/06 |
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Tag: | GEMs; Glycolysis; HCC marker; Mitochondrial ROS; Oxidative phosphorylation |
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Volume: | 78 |
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Issue: | 21-22 |
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Page Number: | 17 |
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First Page: | 7025 |
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Last Page: | 7041 |
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Note: | Open Access funding enabled and organized by Projekt DEAL. This work was funded by the Deutsche Forschungsgemeinschaft (WE 5825/2-1 and CRC 1039, TP B04, B06, Z01). |
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HeBIS-PPN: | 512616094 |
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Institutes: | Medizin |
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Dewey Decimal Classification: | 5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie |
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| 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
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Sammlungen: | Universitätspublikationen |
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Licence (German): | Creative Commons - CC BY - Namensnennung 4.0 International |
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