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DOI: 10.1055/s-0040-1716197
Molecular cross-talk between Y5-receptor and neuropeptide Y drives liver cancer
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.
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Publication History
Article published online:
08 September 2020
© Georg Thieme Verlag KG
Stuttgart · New York