Background: Urokinase type plasminogen activator (uPA) is a 53-kDa serine protease
initially synthesized as a catalytically inactive single chain polypeptide. Inactive-uPA is subject to
proteolytic cleavage, which results in the two-chain active protein. uPA plays key roles in the enhancement
of cell malignancy during tumor progression.
Objectives: The main objective of this review was to analyze and describe the main molecular
mechanisms involved in the regulation of uPA expression in cancer
Methods: Searching literature to evaluate and define the relevant information regarding to the state
of the arts on uPA functionality and regulation in cancer, including intracellular signaling regulation,
tumor progression, invasion, epigenetic mechanism, and finally uPA as therapeutic target in
Results: uPA expression is dysregulated in tumor cells, which results in increased cellular invasion
capacities reflecting changes in uPA activity and expression during tumor progression. In this review
we discuss the main aspects of uPA, from its capacity to activate plasminogen to plasmin, to
the main intracellular signal transduction mechanisms as well as the epigenetic mechanisms involved
in the regulation of uPA expression, including regulation by microRNAs. As well as, the
current therapeutic methodologies targeting uPA for cancer treatment are described.
Conclusion: Although, uPA is dysregulate in tumor progression, its expression is finely regulated
at both enzymatic activity and at protein expression as well, which allow cancer cells efficiently
survive, proliferate, and spread into neighbouring tissues and distant organs. Moreover, since uPA
implications in tumor development and cancer cell invasion and metastasis, it is an attractive target
for cancer chemotherapies.