Down-regulation of active HGFA and matriptase as therapeutic targets against cancer

Karoline Cecilie Knudsen List, Ida Axholm, Kiwi Kjøller, Simone Radziejewska Andreasen, Gloire Irakunda & Rikke Svendsen

Studenteropgave: Bachelorprojekt

Abstrakt

The cellular mesenchymal-epithelial transition (c-MET) receptor is activated by the hepatocyte growth factor (HGF). The proform of HGF (pro-HGF) is cleaved and activated by the serine proteases matriptase and hepatocyte growth factor activator (HGFA). Only the active form of HGF is able to activate the c-MET receptor and. Matriptase and HGFA are inhibited by the HGF activator inhibitors (HAI-1 and -2), which are encoded by the serine protease inhibitor kunitz type 1 and -2 (SPINT1 and -2) genes. An enhanced activation of the c-MET receptor is associated with increased cell proliferation, angiogenesis, invasion, and metastasis in cancer. The aim of this literature review is to examine how the ratio between active matriptase/HGFA and HAI-1 and -2 is disrupted in cancer, and what the therapeutic potentials of matriptase, HGFA, HAI-1 and -2 are. Based on in vitro studies we hypothesize that one mechanism leading to this disruption is due to change in pH and the oxidative conditions, which influence the activation of HGFA and matriptase. However, it might be difficult to control these environmental factors and the potential of selective protease inhibitors is therefore also discussed. Further, the disruption is likely to be caused by hypermethylation of SPINT1 and -2. As treatment against cancer, it might be possible to demethylate the SPINT genes or to directly inject HAI proteins and/or synthetic constructed protease inhibitors. Further investigations are needed before it is possible to conclude whether matriptase, HGFA, HAI-1 and -2 are efficient as therapeutic targets in cancer.

UddannelserBasis - Naturvidenskabelig Bacheloruddannelse, (Bachelor uddannelse) Bachelor
SprogEngelsk
Udgivelsesdato26 maj 2016
Antal sider61

Emneord

  • HAI
  • matriptase
  • HGFA
  • HGF
  • c-MET
  • cancer
  • DAC
  • AZA
  • epigenetic
  • SPINT
  • protease
  • protease inhibitor