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

• Applicant: Professor Dr. Claus Hellerbrand
• Subject Area: Hematology, Oncology
• Term: from 2011 to 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 190230491

• Final Report Year: 2019

Final Report Abstract

This project identified GLUT1 expression and corresponding glycolysis and lactate secretion as critical factor for the crosstalk between HSC and HCC cells. Our data show the potential of GLUT1 as marker for tumor progression and response to therapy. Furthermore, our data indicate the potential of GLUT1 as a therapeutic target in the therapy of primary and secondary liver cancer - alone or in combination with other forms of (chemo)therapy.

Publications

• (2011) Analysis of a promoter polymorphism of the GLUT1 gene in patients with hepatocellular carcinoma. Mol Membr Biol. 28:182-6
  Amann T, Kirovski G, Bosserhoff AK, Hellerbrand C
  (See online at https://doi.org/10.3109/09687688.2011.554447)
• (2011) Downregulation of methylthioadenosine phosphorylase induces progression of hepatocellular carcinoma via accumulation of 5'-deoxy-5'- methylthioadenosine. Am J Pathol. 178:1145-52
  Kirovski G, Stevens AP, Czech B, Dettmer K, Weiss TS, Wild P, Hartmann A, Bosserhoff AK, Oefner PJ, Hellerbrand C
  (See online at https://doi.org/10.1016/j.ajpath.2010.11.059)
• (2012) Hop bitter acids inhibit tumorigenicity of hepatocellular carcinoma cells in vitro. Oncol Rep. 28(4):1423-8
  Saugspier M, Dorn C, Czech B, Gehrig M, Heilmann J, Hellerbrand C
  (See online at https://doi.org/10.3892/or.2012.1925)
• Expression and function of methylthioadenosine phosphorylase in chronic liver disease. PLoS One. 2013; 8(12):e80703
  Czech B, Dettmer K, Valletta D, Saugspier M, Koch A, Stevens AP, Thasler WE, Müller M, Oefner PJ, Bosserhoff AK, Hellerbrand C
  (See online at https://doi.org/10.1371/journal.pone.0080703)
• (2014) Cylindromatosis gene CYLD regulates hepatocyte growth factor expression in hepatic stellate cells through interaction with histone deacetylase 7. Hepatology.; 60(3):1066-81
  Pannem RR, Dorn C, Hellerbrand C, Massoumi R
  (See online at https://doi.org/10.1002/hep.27209)
• (2014) Downregulation of P-cadherin expression in hepatocellular carcinoma induces tumorigenicity. Int J Clin Exp Pathol. 7(9):6125-32
  Bauer R, Valletta D, Bauer K, Thasler WE, Hartmann A, Müller M, Reichert TE, Hellerbrand C
  
• (2014) Regulation and function of the atypical cadherin FAT1 in hepatocellular carcinoma. Carcinogenesis. 35(6):1407-15
  Valletta D, Czech B, Spruss T, Ikenberg K, Wild P, Hartmann A, Weiss TS, Oefner PJ, Müller M, Bosserhoff AK, Hellerbrand C
  (See online at https://doi.org/10.1093/carcin/bgu054)
• (2015) Causal Modeling of Cancer-Stromal Communication Identifies PAPPA as a Novel Stroma-Secreted Factor Activating NFκB Signaling in Hepatocellular Carcinoma. PLoS Comput Biol. 11(5):e1004293
  Engelmann JC, Amann T, Ott-Rötzer B, Nützel M, Reinders Y, Reinders J, Thasler WE, Kristl T, Teufel A, Huber CG, Oefner PJ, Spang R, Hellerbrand C
  (See online at https://doi.org/10.1371/journal.pcbi.1004293)
• (2015) Glucose transporter isoform 1 expression enhances metastasis of malignant melanoma cells. Oncotarget. 6(32):32748-60
  Koch A, Lang SA, Wild PJ, Gantner S, Mahli A, Spanier G, Berneburg M, Müller M, Bosserhoff AK, Hellerbrand C
  (See online at https://doi.org/10.18632/oncotarget.4977)
• (2015). mTOR inhibition improves fibroblast growth factor receptor targeting in hepatocellular carcinoma. Br J Cancer. 2015; 112(5):841-50
  Scheller T, Hellerbrand C, Moser C, Schmidt K, Kroemer A, Brunner SM, Schlitt HJ, Geissler EK, Lang SA
  (See online at https://doi.org/10.1038/bjc.2014.638)
• (2017) Analysis of molecular mechanisms of 5-fluorouracil-induced steatosis and inflammation in vitro and in mice. Oncotarget. 8(8):13059-13072
  Sommer J, Mahli A, Freese K, Schiergens TS, Kuecuekoktay FS, Teufel A, Thasler WE, Müller M, Bosserhoff AK, Hellerbrand C
  (See online at https://doi.org/10.18632/oncotarget.14371)
• (2017) Effect of melanoma cells on proliferation and migration of activated hepatic stellate cells in vitro. Pathol Res Pract. 213(4):400-404
  Meyer T, Koch A, Ebert EV, Czech B, Mueller M, Bosserhoff A, Lang SA, Hellerbrand C
  (See online at https://doi.org/10.1016/j.prp.2016.12.014)
• (2018) ERK activation and autophagy impairment are central mediators of irinotecan-induced steatohepatitis. Gut. 67(4):746-756
  Mahli A, Saugspier M, Koch A, Sommer J, Dietrich P, Lee S, Thasler R, Schulze-Luehrmann J, Luehrmann A, Thasler WE, Müller M, Bosserhoff A, Hellerbrand C
  (See online at https://doi.org/10.1136/gutjnl-2016-312485)
• (2018) Hepatocellular carcinoma cells surviving doxorubicin treatment exhibit increased migratory potential and resistance to doxorubicin retreatment in vitro. Oncol Lett. 15(4):4635-4640
  Buschauer S, Koch A, Wiggermann P, Müller M, Hellerbrand C
  (See online at https://doi.org/10.3892/ol.2018.7887)
• (2018) Wild type Kirsten rat sarcoma is a novel microRNA-622-regulated therapeutic target for hepatocellular carcinoma and contributes to sorafenib resistance. Gut. 67(7):1328-1341
  Dietrich P, Koch A, Fritz V, Hartmann A, Bosserhoff AK, Hellerbrand C
  (See online at https://doi.org/10.1136/gutjnl-2017-315402)