Regulation and role of GLUT1 in hepatocellular carcinoma with focus on the interaction between tumor and activated hepatic stellate cells

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Cirrhosis is the main risk factor for hepatocellular carcinoma (HCC). Activated hepatic stellate cells (HSC) are the cellular source of the excessive matrix deposition and also infiltrate and form the HCC-stroma. We have shown that the expression of the glucose transporter GLUT1 is upregulated in HCC, and herewith, glycolysis, lactate secretion and tumorigenicity of HCC-cells is increased. Furthermore, we found that lactate induces the expression of protumorigenic factors in HSC. Moreover, we discovered that in addition to HCC cells also HSC express GLUT1. In this project we aim to further clarify the role of GLUT1 in hepatocancerogenesis and to analyze the role of GLUT1 in HSC for HCC development and progression. The ultimate aim of this project is to assess the potential of GLUT1 and factors, which affect GLUT1 and the metabolic HCC-HSC-interaction, respectively, as a novel prognostic markers and therapeutic targets in HCC.