Molecular crosstalk between Y5 receptor and neuropeptide Y drives liver cancer

被引：30

作者：

Dietrich, Peter ^{[1
,2
]}

Wormser, Laura ^{[1
]}

Fritz, Valerie ^{[1
]}

Seitz, Tatjana ^{[1
]}

De Maria, Monica ^{[3
]}

Schambony, Alexandra ^{[3
]}

Kremer, Andreas E. ^{[2
]}

Guenther, Claudia ^{[2
]}

Itzel, Timo ^{[4
]}

Thasler, Wolfgang E. ^{[5
]}

Teufel, Andreas ^{[4
]}

Trebicka, Jonel ^{[6
]}

Hartmann, Arndt ^{[7
,8
]}

Neurath, Markus F. ^{[2
,8
]}

von Hoersten, Stephan ^{[9
]}

Bosserhoff, Anja K. ^{[1
,8
]}

Hellerbrand, Claus ^{[1
,8
]}

机构：

[1] Friedrich Alexander Univ Erlangen Nurnberg, Emil Fischer Zentrum, Inst Biochem, Fahrstr 17, D-91054 Erlangen, Germany

[2] Friedrich Alexander Univ Erlangen Nurnberg, Univ Hosp Erlangen, Dept Med 1, Erlangen, Germany

[3] Friedrich Alexander Univ Erlangen Nurnberg, Biol Dept, Dev Biol, Erlangen, Germany

[4] Heidelberg Univ, Med Fac Mannheim, Dept Internal Med 2, Mannheim, Germany

[5] Hepacult GmbH, Planegg, Germany

[6] Univ Hosp Bonn, Dept Med 1, Bonn, Germany

[7] Friedrich Alexander Univ Erlangen Nurnberg, Inst Pathol, Erlangen, Germany

[8] Comprehens Canc Ctr Erlangen European Metropolita, Erlangen, Germany

[9] Friedrich Alexander Univ Erlangen Nurnberg, Franz Penzoldt Ctr, Dept Expt Therapy, Erlangen, Germany

来源：

JOURNAL OF CLINICAL INVESTIGATION | 2020年 / 130卷 / 05期

关键词：

GROWTH-FACTOR-BETA; HEPATOCELLULAR-CARCINOMA; GENE-EXPRESSION; THERAPEUTIC TARGET; ARCUATE NUCLEUS; PROTEIN-KINASE; CELLS; ACTIVATION; OBESITY; SYSTEM;

D O I：

10.1172/JCI131919

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Hepatocellular carcinoma (HCC) is clearly age-related and represents one of the deadliest cancer types worldwide. As a result of 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 involved in diverse cancer-related hallmarks including aging and metabolic alterations, but its impact on liver cancer had been unclear. Here, we observed increased expression of NPY5 receptor (Y5R) in HCC, which correlated with tumor growth and survival. Furthermore, we found that its ligand NPY was secreted by peritumorous hepatocytes. Hepatocyte-derived NPY promoted HCC progression by Y5R activation. TGF-beta 1 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 TGF-beta/NPY/Y5R axis and DPP4 represent attractive therapeutic targets for controlling liver cancer progression.

引用

页码：2509 / 2526

页数：18

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