title: In vitro evidence that KLK14 regulates the components of the HGF/Met axis, pro-HGF and HGF-activator inhibitor 1A and 1B.
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.
authors.forename: Janet C
authors.initials: JC
authors.lastname: Reid
authors.forename: Nigel C
authors.initials: NC
authors.lastname: Bennett
authors.forename: Carson R
authors.initials: CR
authors.lastname: Stephens
authors.forename: Melanie L
authors.initials: ML
authors.lastname: Carroll
authors.forename: Viktor
authors.initials: V
authors.lastname: Magdolen
authors.forename: Judith A
authors.initials: JA
authors.lastname: Clements
authors.forename: John D
authors.initials: JD
authors.lastname: Hooper
mesh_terms: D000818:Animals; D017228:Hepatocyte Growth Factor / Q000378:metabolism*; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000378:metabolism; D011498:Protein Precursors / Q000378:metabolism*; D053491:Proteinase Inhibitory Proteins, Secretory / Q000378:metabolism*; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism*; D061987:Sf9 Cells; D018411:Spodoptera
chemical_list: D011498:Protein Precursors; D053491:Proteinase Inhibitory Proteins, Secretory; C086013:pro-hepatocyte growth factor; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met