EGF receptor transactivation by urokinase receptor stimulus through a mechanism involving Src and matrix metalloproteinases
Author
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Guerrero, Javier
Author
dc.contributor.author
Santibáñez, Juan Francisco
es_CL
Author
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González, Alfonso
es_CL
Author
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Martínez Winkler, Jorge
es_CL
Admission date
dc.date.accessioned
2014-01-08T14:49:42Z
Available date
dc.date.available
2014-01-08T14:49:42Z
Publication date
dc.date.issued
2004
Cita de ítem
dc.identifier.citation
Experimental Cell Research 292 (2004) 201– 208. DOI: 10.1016/j.yexcr.2003.08.011
en_US
Identifier
dc.identifier.issn
0014-4827
Identifier
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https://repositorio.uchile.cl/handle/2250/124047
General note
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Artículo de publicación ISI
en_US
Abstract
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Urokinase-type plasminogen activator receptor (uPAR) and epidermal growth factor receptor (EGFR) are ubiquitous receptors involved in
the control of a variety of cellular processes frequently found altered in cancer cells. The EGFR has been recently described to play a
transduction role of uPAR stimuli, mediating uPA-induced proliferation in highly malignant cells that overexpress uPAR. In the present work,
we found for the first time that uPAR stimulation with the amino-terminal fragment (ATF) of urokinase devoid of proteolytic activity
transactivates the EGFR in mammary MCF-7 cells through a mechanism involving Src and a metalloproteinase, as indicated by its sensitivity
to selected inhibitors. In these cells, which express low levels of uPAR and malignancy, both ATF and EGF stimuli induced an interaction of
the EGFR with uPAR and ERK activation. However, EGFR activation by uPAR stimuli mediated cellular invasion rather than proliferation,
while EGFR activation by EGF led to a proliferative response. These results revealed a complex modulation of EGFR function toward
different cellular responses according to the status of uPAR activity. On the other hand, we also found that MMP-mediated activation of
EGFR can occur in an autocrine manner in cells which secrete uPA. All this reveals novel regulatory systems operating through autocrine
loops involving uPAR stimuli, Src, MMP and EGFR activation which could mediate fine control of physiological processes as well as
contribute to the expression of proliferative and invasive phenotypes of cancerous cells.
en_US
Patrocinador
dc.description.sponsorship
This work received financial
support from FONDECYT Grant 1010703 (to JM) and
FONDAP Grant 13980001 (to AG). The Millennium
Institute for Fundamental and Applied Biology (MIFAB)
is financed in part by the Ministerio de Planificacio´n y
Cooperacio´n de Chile.