EGF receptor transactivation by urokinase receptor stimulus through a mechanism involving Src and matrix metalloproteinases

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dc.contributor.authorGuerrero, J
dc.contributor.authorSantibañez, JF
dc.contributor.authorGonzález, A
dc.contributor.authorMartínez, J
dc.date.accessioned2025-01-21T01:08:34Z
dc.date.available2025-01-21T01:08:34Z
dc.date.issued2004
dc.description.abstractUrokinase-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 NIMP-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. (C) 2003 Elsevier Inc. All rights reserved.
dc.fuente.origenWOS
dc.identifier.doi10.1016/j.yexcr.2003.08.011
dc.identifier.eissn1090-2422
dc.identifier.issn0014-4827
dc.identifier.urihttps://doi.org/10.1016/j.yexcr.2003.08.011
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/96483
dc.identifier.wosidWOS:000187777800019
dc.issue.numero1
dc.language.isoen
dc.pagina.final208
dc.pagina.inicio201
dc.revistaExperimental cell research
dc.rightsacceso restringido
dc.subjectEGFR
dc.subjecturokinase receptor
dc.subjectSrc
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleEGF receptor transactivation by urokinase receptor stimulus through a mechanism involving Src and matrix metalloproteinases
dc.typeartículo
dc.volumen292
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
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