Hepsin is a membrane serine protease expressed in several human tissues including the liver, kidney, prostate, and thyroid. In vitro studies have shown that hepsin activates blood clotting factors VII, XII, and IX, pro-urokinase (pro-uPA), and pro-hepatocyte growth factor (pro-HGF)[1]. Hepsin expression was upregulated in prostate cancer tissue samples and cell lines. Inhibition of hepsin attenuated EMT and cell invasion and downregulated the expression of miR-222. Decreased miR-222 expression enhanced the level of PPP2R2A, which in turn attenuated the AKT signaling. Activation of miR-222 or AKT could block the inhibitory effects on EMT and cell invasion induced by hepsin deficiency[2]. Hepsin-induced depletion of cellular HAI-1 led to a sharp increase in pericellular serine protease activity. The derepressed hepsin proteolytically activated downstream serine proteases, augmented HGF/MET signalling and caused deterioration of desmosomes and hemidesmosomes; structures important for cell cohesion and cell-basement membrane interaction[3]. Hepsin expression was found to be significantly higher in endometrial cancer compared to normal endometrium and endometrial hyperplasia. High levels of hepsin expression were associated with advanced stage (p<0.001), high grade (p=0.002), depth of myometrial invasion (p<0.001), cervical involvement (p=0.007), lymph node metastasis (p=0.001), lymph vascular space (LVS) involvement (p=0.006), ovarian metastasis (p=0.002), and peritoneal cytology (p=0.03) of endometrial cancer[4]. Hepln-13 is a potent and orally active Hepsin inhibitor with an IC50 of 0.33 µM. Hepln-13 can be used for the research of metastatic prostate cancer. Hepln-13 (10 µM; 2 hours; 293 cells) inhibits cleavage. HepIn-13 displays dose dependent inhibition of Hepsin overexpression-relevant prostate cancer phenotypes and blocks prostate cancer metastasis[5].
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