Unlike in normal epithelium, dysregulated overactivation of various proteases have been
reported in cancers. Degradation of pericancerous extracellular matrix leading to cancer cell invasion
by matrix metalloproteases is well known evidence. On the other hand, several cell-surface proteases,
including type II transmembrane serine proteases (TTSPs), also induce progression through activation
of growth factors, protease activating receptors and other proteases. Hepatocyte growth factor
(HGF) known as a multifunctional growth factor that upregulates cancer cell motility, invasiveness,
proliferative, and anti-apoptotic activities through phosphorylation of MET (a specific receptor of
HGF). HGF secreted as inactive zymogen (pro-HGF) from cancer associated stromal fibroblasts,
and the proteolytic activation by several TTSPs including matriptase and hepsin is required. The
activation is strictly regulated by HGF activator inhibitors (HAIs) in physiological condition. However,
downregulation is frequently observed in cancers. Indeed, overactivation of MET by upregulation of
matriptase and hepsin accompanied by the downregulation of HAIs in urological cancers (prostate
cancer, renal cell carcinoma, and bladder cancer) are also reported, a phenomenon observed in cancer
cells with malignant phenotype, and correlated with poor prognosis. In this review, we summarized
current reports focusing on TTSPs, HAIs, and MET signaling axis in urological cancers.
Subfamily | Protease |
---|---|
HAT/DESC | HAT |
DESC1 | |
TMPRSS 11A | |
HAT-like 4 | |
HAT-like 5 | |
Hepsin/TMPRSS | Hepsin (TMPRSS1) |
TMPRSS 2 | |
TMPRSS 3 | |
TMPRSS 4 | |
TMPRSS 13 | |
Enteropeptidase | |
Spinesin | |
Matriptase | Matriptase |
Matriptase 2 | |
Matriptase 3 | |
Polyserase | |
Corin | Corin |
This entry is adapted from the peer-reviewed paper 10.3390/ijms21082663