Z Gastroenterol 2020; 58(08): e174
DOI: 10.1055/s-0040-1716197
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Molecular cross-talk between Y5-receptor and neuropeptide Y drives liver cancer

P Dietrich
1   Universitätsklinikum Erlangen, Medizin 1, Erlangen, Deutschland
2   Institut für Biochemie, Biochemie und Molekulare Medizin, Erlangen, Deutschland
,
L Wormser
2   Institut für Biochemie, Biochemie und Molekulare Medizin, Erlangen, Deutschland
,
V Fritz
2   Institut für Biochemie, Biochemie und Molekulare Medizin, Erlangen, Deutschland
,
T Seitz
2   Institut für Biochemie, Biochemie und Molekulare Medizin, Erlangen, Deutschland
,
M de Maria
3   Developmental Biology, Biology Department, Erlangen, Deutschland
,
A Schambony
3   Developmental Biology, Biology Department, Erlangen, Deutschland
,
A Kremer
1   Universitätsklinikum Erlangen, Medizin 1, Erlangen, Deutschland
,
C Günther
1   Universitätsklinikum Erlangen, Medizin 1, Erlangen, Deutschland
,
T Itzel
4   Universität Heidelberg, Department of Internal Medicine II, Mannheim, Deutschland
,
W Thasler
5   Hepacult GmbH, Planegg/Martinsried, Deutschland
,
A Teufel
4   Universität Heidelberg, Department of Internal Medicine II, Mannheim, Deutschland
,
J Trebicka
6   Universitätsklinikum Bonn, Department of Medicine I, Bonn, Deutschland
,
A Hartmann
7   Universitätsklinikum Erlangen, Institut für Pathologie, Erlangen, Deutschland
,
M Neurath
1   Universitätsklinikum Erlangen, Medizin 1, Erlangen, Deutschland
,
S von Hörsten
8   Franz-Penzoldt-Center, Department of Experimental Therapy, Erlangen, Deutschland
,
A Bosserhoff
2   Institut für Biochemie, Biochemie und Molekulare Medizin, Erlangen, Deutschland
,
C Hellerbrand
2   Institut für Biochemie, Biochemie und Molekulare Medizin, Erlangen, Deutschland
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Background Hepatocellular carcinoma (HCC) is clearly age-related and represents one of the deadliest cancer types worldwide. Due to globally increasing risk factors including metabolic disorders, the incidence rates of HCC are still rising. However, the molecular hallmarks of HCC remain poorly understood.

Aim Neuropeptide Y (NPY) and NPY-receptors represent a highly conserved, stress-activated system which is involved in diverse cancer-related hallmarks including aging and metabolic alterations, but its impact on liver cancer had been unclear.

Results Here, we observed increased NPY5-receptor (Y5R) expression in HCC which correlated with tumor growth and survival. Furthermore, we found that its ligand NPY was secreted by peri-tumorous hepatocytes. Hepatocyte-derived NPY promoted HCC progression byY5R-activation. Transforming growth factor beta 1 (TGFβ1) was identified as a regulator of NPY in hepatocytes and induced Y5R in invasive cancer cells. Moreover, NPY-conversion by dipeptidylpeptidase 4 (DPP4) augmented Y5R-activation and function in liver cancer.

Conclusion The TGFβ-NPY-Y5R-axis and DPP4 represent attractive therapeutic targets for controlling liver cancer progression.



Publication History

Article published online:
08 September 2020

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