PMID- 14720519
OWN - NLM
STAT- MEDLINE
DCOM- 20040227
LR  - 20190707
IS  - 0014-4827 (Print)
IS  - 0014-4827 (Linking)
VI  - 292
IP  - 1
DP  - 2004 Jan 1
TI  - EGF receptor transactivation by urokinase receptor stimulus through a mechanism 
      involving Src and matrix metalloproteinases.
PG  - 201-8
AB  - 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.
FAU - Guerrero, Javier
AU  - Guerrero J
AD  - Laboratorio de Biologia Celular, INTA, Universidad de Chile, Santiago 11, Chile.
FAU - Santibanez, Juan Francisco
AU  - Santibanez JF
FAU - Gonzalez, Alfonso
AU  - Gonzalez A
FAU - Martinez, Jorge
AU  - Martinez J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Exp Cell Res
JT  - Experimental cell research
JID - 0373226
RN  - 0 (PLAUR protein, human)
RN  - 0 (Peptide Fragments)
RN  - 0 (Quinazolines)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Receptors, Urokinase Plasminogen Activator)
RN  - 0 (Tyrphostins)
RN  - 170449-18-0 (RTKI cpd)
RN  - 62229-50-9 (Epidermal Growth Factor)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 3.4.21.73 (Urokinase-Type Plasminogen Activator)
RN  - EC 3.4.24.- (Matrix Metalloproteinases)
SB  - IM
MH  - Adenocarcinoma/pathology
MH  - Breast Neoplasms/*metabolism/pathology
MH  - Cell Division
MH  - Cell Line, Tumor
MH  - Cell Movement
MH  - Epidermal Growth Factor/metabolism/pharmacology
MH  - ErbB Receptors/*metabolism
MH  - Female
MH  - Genes, src/*physiology
MH  - Humans
MH  - Kinetics
MH  - Matrix Metalloproteinases/*metabolism
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - Neoplasm Invasiveness/pathology
MH  - Peptide Fragments/chemistry/drug effects/metabolism/pharmacology
MH  - Phosphorylation/drug effects
MH  - Quinazolines
MH  - Receptors, Cell Surface/*metabolism
MH  - Receptors, Urokinase Plasminogen Activator
MH  - *Transcriptional Activation
MH  - Tyrphostins/pharmacology
MH  - Urokinase-Type Plasminogen Activator/chemistry
EDAT- 2004/01/15 05:00
MHDA- 2004/02/28 05:00
CRDT- 2004/01/15 05:00
PHST- 2004/01/15 05:00 [pubmed]
PHST- 2004/02/28 05:00 [medline]
PHST- 2004/01/15 05:00 [entrez]
AID - S0014482703004658 [pii]
AID - 10.1016/j.yexcr.2003.08.011 [doi]
PST - ppublish
SO  - Exp Cell Res. 2004 Jan 1;292(1):201-8. doi: 10.1016/j.yexcr.2003.08.011.