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Research Projects – uPAR in Cancer Progression

The receptor for urokinase-type plasminogen activator (uPAR) binds the serine protease and plasminogen activator, uPA, with high affinity. Although uPA and uPAR were first recognized for their ability to activate plasminogen near the cell-surface, we now understand that uPAR is a central component of a potent cell-signaling receptor system. In multiple forms of human malignancy, uPAR expression is correlated with cancer progression. Our goal is to understand the cell-signaling cascades activated downstream of uPAR, which may contribute to the effects of this receptor on cancer progression. We focus on pro-survival cell-signaling pathways, Rho family GTPases, and other cell-signaling factors involved in cell migration. We also are interested in understanding receptors such as the EGF Receptor that function together with uPAR to trigger cell-signaling. Our work has already shown that uPAR-initiated cell-signaling promotes epithelial-mesenchymal transition in cancer cells and cancer stem cell-like properties. Induction of uPAR expression may constitute an important pathway by which tumors become resistant to targeted anticancer drugs in neoplasms such as glioblastoma. The figure on this page shows a confocal fluorescence microscopy image of a glioblastoma neurosphere, which is enriched in uPAR-expressing tumor-initiating cells.