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Urokinase Type Plasminogen Activator and the Molecular Mechanisms of its Regulation in Cancer

[ Vol. 24 , Issue. 10 ]

Author(s):

Juan F. Santibanez*   Pages 936 - 946 ( 11 )

Abstract:


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 cancer.

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.

Keywords:

uPA, urokinase type plasminogen activator, uPAR, urokinase type plasminogen activator receptor, cancer, signaling, epigenetic, microRNA, therapies.

Affiliation:

Group for Molecular Oncology, Institute for Medical Research (IMI), University of Belgrade, Dr. Subotica 4, 11129 Belgrade

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