Molecular cross-talk between Y5-receptor and neuropeptide Y drives liver cancer

Dietrich P, Wormser L, Fritz V, Seitz T, de Maria M, Schambony A, Kremer A, Günther C, Itzel T, Thasler WE, Teufel A, Trebicka J, Hartmann A, Neurath M, von Hörsten S, Boßerhoff AK, Hellerbrand C (2020)

Publication Language: English

Publication Type: Journal article

Publication year: 2020

Journal

Journal of Clinical Investigation American Society for Clinical Investigation

Book Volume: 130

Pages Range: 2509-2526

Journal Issue: 5

DOI: 10.1172/JCI131919

Abstract

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

Authors with CRIS profile

Peter Dietrich Lehrstuhl für Biochemie und Molekulare Medizin Laura Wormser Lehrstuhl für Biochemie und Molekulare Medizin Valerie Fritz Lehrstuhl für Biochemie und Molekulare Medizin Tatjana Seitz Professur für Biochemie und Molekulare Pathobiologie Monica de Maria Lehrstuhl für Entwicklungsbiologie Alexandra Schambony Lehrstuhl für Entwicklungsbiologie Andreas Kremer Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Claudia Günther Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Arndt Hartmann Lehrstuhl für Allgemeine Pathologie und Pathologische Anatomie Markus Neurath Lehrstuhl für Innere Medizin I Stephan von Hörsten Professur für Experimentelle Biomedizin Anja Katrin Boßerhoff Lehrstuhl für Biochemie und Molekulare Medizin Claus Hellerbrand Professur für Biochemie und Molekulare Pathobiologie

Additional Organisation(s)

Interdisziplinäres Zentrum für Klinische Forschung

Related research project(s)

D032: The role of neuropeptide Y in chemo-resistance and immune checkpoint inhibition in hepatocellular carcinoma March 1, 2020 - Feb. 28, 2023

Involved external institutions

Medizinische Fakultät Mannheim der Universität Heidelberg DE Germany (DE) Hepacult GmbH DE Germany (DE) Universitätsklinikum Bonn DE Germany (DE)

How to cite

APA:

Dietrich, P., Wormser, L., Fritz, V., Seitz, T., de Maria, M., Schambony, A.,... Hellerbrand, C. (2020). Molecular cross-talk between Y5-receptor and neuropeptide Y drives liver cancer. Journal of Clinical Investigation, 130(5), 2509-2526. https://doi.org/10.1172/JCI131919

MLA:

Dietrich, Peter, et al. "Molecular cross-talk between Y5-receptor and neuropeptide Y drives liver cancer." Journal of Clinical Investigation 130.5 (2020): 2509-2526.

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