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One in nine women will be diagnosed with breast cancer. A significant percentage of women will already have metastatic cancers at the time of diagnosis and even though the 5-year survival rates have improved, a majority of women will still succumb to recurrent disease. To develop metastatic disease, the extracellular matrix surrounding the cancer must be degraded, allowing cancer cells to travel to distant sites. Matrix degradation is mediated by proteases, one of which is urokinase plasminogen activator (uPA). A specific inhibitor, plasminogen activator inhibitor-1 (PAI-1), regulates uPA activity. Surprisingly, an elevated level of PAI-1 is a poor prognostic factor for breast cancer patients. It is unclear why a substance that blocks matrix degradation would be linked to a poor prognosis. Our objective is to understand the “paradox” of why too much PAI-1 is detrimental to women with breast cancer. We believe that expression of PAI-1 confers a survival advantage upon breast cancer cells. Our results will shed valuable information on the role of PAI-1 in one of the most significant problems hindering the treatment of women with breast cancer, invasion and metastasis.
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OPEN LIFE SCIENCESno. 1 (2022): 599-609
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