The urokinase plasminogen activator system, which is a serine protease family include urokinase-type plasminogen activator (uPA), the uPA receptor and plasminogen activator inhibitors (PAIs). uPA catalyzes the transformation of plasminogen to its active form plasmin, which is able to degrade the extracellular matrix (ECM) and basement membranes, directly or indirectly through activating pro-matrix metalloproteinases (pro-MMPs), promoting cancer cell metastasis and invasion.
Results from these studies provide direct evidence for an enhancing role of uPA in malignant invasion and experimental metastasis and for a modulatory role of PAI-1 in tumor cell-mediated breakdown of extracellular matrices.
The binding of uPA with uPAR is instrumental for the activation of plasminogen to plasmin, which in turn initiates a series of proteolytic cascade to degrade the components of the extracellular matrix, and thereby, cause tumor cell migration from the primary site of origin to a distant secondary organ.
Our data clearly suggest that by binding to uPA promoter elements, Rel transcripton factors contribute directly to elevated uPA gene expression in human ovarian cancer cells, thereby promoting the multiple functions of uPA during tumor growth and metastasis.
Because beta-catenin and its target genes urokinase-type plasminogen activator receptor (uPAR) and cyclin D1 are overexpressed in colon cancers, and are linked to cancer growth, invasion, and metastasis, we investigated whether DCA activates beta-catenin signaling and promotes colon cancer cell growth and invasiveness.
In vivo and in vitro experimental models have suggested a major role for the urokinase-type plasminogen activator (uPA) in tumor cell invasion and metastasis.
The urokinase-type plasminogen activator (uPA) plays a central role in tissue remodelling events occurring in normal physiology and in pathophysiology, including cancer invasion and metastasis.
In turn, uPA participates in the activation of secreted latent TGF-β, thus producing a malicious loop which contributes to tumor progression and metastasis.
These results suggest that at least one of the underlying mechanisms of BRMS1-dependent suppression of tumor metastasis includes inhibition of NF-kappaB activity and subsequent suppression of uPA expression in breast cancer and melanoma cells.
Urokinase-type plasminogen activator (uPA) plays a central role in many aspects of cellular regulation, such as fibrinolysis, cell migration, and metastasis.
Therefore, sex steroidal induction of PAI-1 might contribute to the inhibition of invasion and metastasis, concomitantly with the inhibition of neovascularization associated with tPA and uPA activities, in well differentiated endometrial cancer.
The serine protease urokinase-type plasminogen activator, uPA, when bound to its specific receptor, uPAR (CD87), plays a significant role in tumor cell invasion and metastasis.
The results of this study indicated the possibility that cagA-positive H. pylori may play an important role not only in tissue remodeling, angiogenesis and wound healing but also in the process of degradation of the extracellular matrix breakdown, tumor invasion and metastasis by inducing uPA and uPAR complex in the gastric cancer cells.
By comparing the two groups, u-PA and VEGF were positively correlated in gastric cancer tissue (P < 0.05). u-PA and VEGF were highly expressed in gastric cancer tissue, which could be used as the molecular biological indicators to predict the invasion and metastasis potential of gastric cancer.
C4.4A, a structural homologue of the urokinase-type plasminogen activator receptor (uPAR), was originally identified as a metastasis-associated membrane protein, but little is known about its structural and functional properties.
It is a specific cell surface receptor for its ligand, urokinase-type plasminogen activator, which catalyzes the formation of plasmin from plasminogen to generate the proteolytic cascade and leads to the breakdown of the extracellular matrix. uPAR has been shown to correlate with a propensity to tumor invasion and metastasis in several types of non-central nervous system tumors.
SCH66336 treatment also reduced the expression and activity of the urokinase-type plasminogen activator (uPA) and matrix metalloproteinase 2 (MMP-2), both important regulators of tumor metastasis.