Format

Send to

Choose Destination
Sci Rep. 2016 Mar 14;6:22996. doi: 10.1038/srep22996.

Inhibition of renalase expression and signaling has antitumor activity in pancreatic cancer.

Author information

1
Department of Medicine, VACHS, Yale University School of Medicine, New Haven, CT 06520, USA.
2
Department of Surgery, University of Connecticut, Farmington, CT 06032, USA.
3
Renal Division, Renji hospital, Shanghai Jiaotong Univ School of Medicine, Shanghai, China.
4
Department of Surgery, VACHS, Yale University, New Haven, CT 06520, USA.

Abstract

An essential feature of cancer is dysregulation of cell senescence and death. Renalase, a recently discovered secreted flavoprotein, provides cytoprotection against ischemic and toxic cellular injury by signaling through the PI3K-AKT and MAPK pathways. Here we show that renalase expression is increased in pancreatic cancer tissue and that it functions as a growth factor. In a cohort of patients with pancreatic ductal adenocarcinoma, overall survival was inversely correlated with renalase expression in the tumor mass, suggesting a pathogenic role for renalase. Inhibition of renalase signaling using siRNA or inhibitory anti-renalase antibodies decreased the viability of cultured pancreatic ductal adenocarcinoma cells. In two xenograft mouse models, either the renalase monoclonal antibody m28-RNLS or shRNA knockdown of renalase inhibited pancreatic ductal adenocarcinoma growth. Inhibition of renalase caused tumor cell apoptosis and cell cycle arrest. These results reveal a previously unrecognized role for the renalase in cancer: its expression may serve as a prognostic maker and its inhibition may provide an attractive therapeutic target in pancreatic cancer.

PMID:
26972355
PMCID:
PMC4789641
DOI:
10.1038/srep22996
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center