Author:
Reid Janet C.,Bennett Nigel C.,Stephens Carson R.,Carroll Melanie L.,Magdolen Viktor,Clements Judith A.,Hooper John D.
Abstract
Abstract
Kallikrein-related peptidase (KLK) 14 is a serine protease linked to several pathologies including prostate cancer. We show that KLK14 has biphasic effects in vitro on activating and inhibiting components of the prostate cancer associated hepatocyte growth factor (HGF)/Met system. At 5–10 nm, KLK14 converts pro-HGF to the two-chain heterodimer required for Met activation, while higher concentrations degrade the HGF α-chain. HGF activator-inhibitor (HAI)-1A and HAI-1B, which inhibit pro-HGF activators, are degraded by KLK14 when protease:inhibitor stoichiometry is 1:1 or the protease is in excess. When inhibitors are in excess, KLK14 generates HAI-1A and HAI-1B fragments known to inhibit pro-HGF activating serine proteases. These in vitro data suggest that increased KLK14 activity could contribute at multiple levels to HGF/Met-mediated processes in prostate and other cancers.
Funder
National Health and Medical Research Council
Cancer Council Queensland
Prostate Cancer Foundation of Australia
Australian Research Council
Subject
Clinical Biochemistry,Molecular Biology,Biochemistry
Reference100 articles.
1. Pericellular activation of hepatocyte growth factor by the transmembrane serine proteases matriptase and hepsin, but not by the membrane-associated protease uPA;Biochem. J.,2010
2. Expression of bFGF, VEGF and c-met and their correlation with microvessel density and progression in prostate carcinoma;Anticancer Res.,2004
3. Addition of beta1–6 GlcNAc branching to the oligosaccharide attached to Asn 772 in the serine protease domain of matriptase plays a pivotal role in its stability and resistance against trypsin;Glycobiology,2004
4. Matriptase activation and shedding with HAI-1 is induced by steroid sex hormones in human prostate cancer cells, but not in breast cancer cells;Am. J. Physiol. Cell Physiol.,2006
5. Mechanisms of hepatocyte growth factor activation in cancer tissues;Cancers (Basel),2014
Cited by
7 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献