Molecular crosstalk between Y5 receptor and neuropeptide Y drives liver cancer.
Aging
Cancer
Hepatology
Journal
The Journal of clinical investigation
ISSN: 1558-8238
Titre abrégé: J Clin Invest
Pays: United States
ID NLM: 7802877
Informations de publication
Date de publication:
01 05 2020
01 05 2020
Historique:
received:
18
07
2019
accepted:
23
01
2020
pubmed:
31
1
2020
medline:
27
1
2021
entrez:
31
1
2020
Statut:
ppublish
Résumé
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-β1 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-β/NPY/Y5R axis and DPP4 represent attractive therapeutic targets for controlling liver cancer progression.
Identifiants
pubmed: 31999643
pii: 131919
doi: 10.1172/JCI131919
pmc: PMC7190991
doi:
pii:
Substances chimiques
Neoplasm Proteins
0
Neuropeptide Y
0
Receptors, Neuropeptide Y
0
neuropeptide Y5 receptor
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2509-2526Références
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