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

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

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


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.

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