The urokinase plasminogen activator system in breast cancer invasion and metastasis

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. Both uPA and PAI-1 are poor prognosis markers in primary breast cancer. Evidence has been presented that the uPA system facilitates breast cancer metastasis by several different mechanisms, such as the Ras-ERK pathway and p38 MAPK pathway. This review focuses on uPA system, summarizes their biological effects, highlights the molecular mechanism and pathway, and discusses the role of uPA system in the prevention and treatment of human breast cancers.