Regulation und Rolle von GLUT1 im hepatozellulären Karzinom unter Fokussierung auf die Interaktion zwischen Tumorzellen und aktivierten hepatischen Sternzellen

• Antragsteller: Professor Dr. Claus Hellerbrand
• Fachliche Zuordnung: Hämatologie, Onkologie
• Förderung: Förderung von 2011 bis 2018
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 190230491

• Erstellungsjahr: 2019

Zusammenfassung der Projektergebnisse

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.

Projektbezogene Publikationen (Auswahl)

• (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
  (Siehe online unter 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
  (Siehe online unter 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
  (Siehe online unter 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
  (Siehe online unter 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
  (Siehe online unter 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
  (Siehe online unter 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
  (Siehe online unter 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
  (Siehe online unter 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
  (Siehe online unter 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
  (Siehe online unter 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
  (Siehe online unter 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
  (Siehe online unter 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
  (Siehe online unter 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
  (Siehe online unter https://doi.org/10.1136/gutjnl-2017-315402)