Volume 2013 (2013), Article ID 598251, 7 pages
Human Sprouty1 Suppresses Urokinase Receptor-Stimulated Cell Migration and Invasion
Department of Surgery, Cancer Research Laboratories, University of New South Wales, Sydney, NSW 2217, Australia
Received 5 July 2013; Accepted 13 August 2013
Academic Editors: H. Himeno, D. Hoja-Lukowicz, Y. Ihara, T. Kietzmann, and F. Lesage
Copyright © 2013 Ahmed H. Mekkawy and David L. Morris. 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.
The urokinase-type plasminogen activator receptor (uPAR) has been implicated in several processes in tumor progression including cell migration and invasion in addition to initiation of signal transduction. Since uPAR lacks a transmembrane domain, it uses the interaction with other proteins to modulate intracellular signal transduction. We have previously identified hSpry1 as a partner protein of uPAR, suggesting a physiological role for hSpry1 in the regulation of uPAR signal transduction. In this study, hSpry1 was found to colocalize with uPAR upon stimulation with epidermal growth factor (EGF), urokinase (uPA), or its amino terminal fragment (uPA-ATF), implicating a physiological role of hSpry1 in regulation of uPAR signalling pathway. Moreover, hSpry1 was able to inhibit uPAR-stimulated cell migration in HEK293/uPAR, breast carcinoma, and colorectal carcinoma cells. In addition, hSpry1 was found to inhibit uPAR-stimulated cell invasion in breast carcinoma and osteosarcoma cell lines. Increasing our understanding of how hSpry1 negatively regulates uPAR-stimulated cellular functions may determine a distinctive role for hSpry1 in tumour suppression.