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@ARTICLE{Jennemann:181227,
      author       = {R. Jennemann$^*$ and G. Federico$^*$ and D. Mathow$^*$ and
                      M. Rabionet$^*$ and F. Rampoldi$^*$ and Z. Popovic$^*$ and
                      M. Volz$^*$ and T. Hielscher$^*$ and R. Sandhoff$^*$ and
                      H.-J. Gröne$^*$},
      title        = {{I}nhibition of hepatocellular carcinoma growth by blockade
                      of glycosphingolipid synthesis.},
      journal      = {OncoTarget},
      volume       = {8},
      number       = {65},
      issn         = {1949-2553},
      address      = {[S.l.]},
      publisher    = {Impact Journals LLC},
      reportid     = {DKFZ-2022-01875},
      pages        = {109201 - 109216},
      year         = {2017},
      note         = {POF Topic: 317},
      abstract     = {Hepatocellular carcinoma (HCC) is one of the most frequent
                      cancers. In vitro studies suggest that growth and response
                      to therapy of human carcinomas may depend on
                      glycosphingolipid (GSL) expression. Glucosylceramide
                      synthase (GCS), encoded by the gene Ugcg, is the basic
                      enzyme required for the synthesis of GSLs. Gene array
                      analysis implied that Ugcg is significantly overexpressed in
                      human HCC as compared to non-tumorous liver tissue.
                      Therefore we have investigated whether tumor - genesis and -
                      growth is altered in the absence of GSLs. An endogenous
                      liver cancer model has been initiated by application of
                      diethylnitrosamine in mice lacking Ugcg specifically in
                      hepatocytes. We have now shown that hepatocellular tumor
                      initiation and growth in mice is significantly inhibited by
                      hepatic GSL deficiency in vivo. Neither the expression of
                      cell cycle proteins, such as cyclins and pathways such as
                      the MAP-kinase/Erk pathway nor the mTOR/Akt pathway as well
                      as the number of liver infiltrating macrophages and T cells
                      were essentially changed in tumors lacking GSLs.
                      Significantly elevated bi-nucleation of atypical
                      hepatocytes, a feature for impaired cytokinesis, was
                      detected in tumors of mice lacking liver-specific GSLs. A
                      reduction of proliferation and restricted growth of tumor
                      microspheres due to delayed, GSL-dependent cytokinesis,
                      analogous to the histopathologic phenotype in vivo could be
                      demonstrated in vitro. GSL synthesis inhibition may thus
                      constitute a potential therapeutic target for hepatocellular
                      carcinoma.},
      keywords     = {cytokinesis (Other) / glycolipid (Other) /
                      glycosphingolipid (Other) / hepatocellular carcinoma (Other)
                      / sphingomyelin (Other)},
      cin          = {G130 / A411 / C060},
      ddc          = {610},
      cid          = {I:(DE-He78)G130-20160331 / I:(DE-He78)A411-20160331 /
                      I:(DE-He78)C060-20160331},
      pnm          = {317 - Translational cancer research (POF3-317)},
      pid          = {G:(DE-HGF)POF3-317},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:29312601},
      pmc          = {pmc:PMC5752514},
      doi          = {10.18632/oncotarget.22648},
      url          = {https://inrepo02.dkfz.de/record/181227},
}