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ISRN Dermatology
Volume 2013 (2013), Article ID 597927, 26 pages
Review Article

Transforming Growth Factor-Beta and Urokinase-Type Plasminogen Activator: Dangerous Partners in Tumorigenesis—Implications in Skin Cancer

Laboratory for Experimental Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, Dr. Subotića 4, 11129 Belgrade, Serbia

Received 26 May 2013; Accepted 18 June 2013

Academic Editors: M. Clelia and E. Nagore

Copyright © 2013 Juan F. Santibanez. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Transforming growth factor-beta (TGF-β) is a pleiotropic factor, with several different roles in health and disease. TGF-β has been postulated as a dual factor in tumor progression, since it represses epithelial tumor development in early stages, whereas it stimulates tumor progression in advanced stages. During tumorigenesis, cancer cells acquire the capacity to migrate and invade surrounding tissues and to metastasize different organs. The urokinase-type plasminogen activator (uPA) system, comprising uPA, the uPA cell surface receptor, and plasminogen-plasmin, is involved in the proteolytic degradation of the extracellular matrix and regulates key cellular events by activating intracellular signal pathways, which together allow cancer cells to survive, thus, enhancing cell malignance during tumor progression. Due to their importance, uPA and its receptor are tightly transcriptionally regulated in normal development, but are deregulated in cancer, when their activity and expression are related to further development of cancer. TGF-β regulates uPA expression in cancer cells, while uPA, by plasminogen activation, may activate the secreted latent TGF-β, thus, producing a pernicious cycle which contributes to the enhancement of tumor progression. Here we review the specific roles and the interplay between TGF-β and uPA system in cancer cells and their implication in skin cancer.