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
  
• (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
  
• (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
  
• 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
  
• (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
  
• (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
  
• (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
  
• (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
  
• (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
  
• (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
  
• (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
  
• (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
  
• (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
  
• (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