Wesley UV, McGroarty M, and Homayouni A. Dipeptidyl Peptidase Inhibits Malignant Phenotype of Prostate Cancer Cells by Blocking bFGF Signaling Pathway. Cancer Res. 2005;65(4);1325-1334.

Abstract: Dipeptidyl peptidase (DPPIV) is a serine protease with tumor suppressor function. It regulates the activities of mitogenic peptides implied in cancer development. Progression of benign prostate cancer (PCa) to malignant metastasis is linked to increased production of basic fibroblast growth factor (bFGF), a powerful mitogen. In this study, using in vitro model system we show that DPPIV loss is associated with increased bFGF production in metastatic PCa cells. DPPIV re-expression in PCa cells blocks nuclear localization of bFGF, reduces bFGF levels, inhibits MAPK-ERK1/2 activation, and decreases levels of urokinase plasminogen activator (uPA), known down-stream effectors of bFGF signaling pathway. These molecular changes were accompanied by induction of apoptosis, cell cycle arrest, inhibition of in vitro cell migration, and invasion. Silencing of DPPIV by siRNA resulted in increased bFGF levels and restoration of MAPK-ERK1/2 activation. These results indicate that DPPIV inhibits the malignant phenotype of PCa cells by blocking bFGF signaling pathway.