EGFR is a transducer of the urokinase receptor initiated signal that is required for in vivo growth of a human carcinoma

David Liu, Julio A. Aguirre Ghiso, Yeriel Estrada, Liliana Ossowski

Research output: Contribution to journalArticlepeer-review

356 Scopus citations

Abstract

Urokinase plasminogen activator receptor (uPAR) activates α5β1 integrin and ERK signaling, inducing in vivo proliferation of HEp3 human carcinoma. Here we demonstrate that EGFR mediates the uPAR/integrin/fibronectin (FN) induced growth pathway. Its activation is ligand-independent and does not require high EGFR, but does require high uPAR expression. Only when uPAR level is constitutively elevated does EGFR become α5β1-associated and activated. Domain 1 of uPAR is crucial for EGFR activation, and FAK links integrin and EGFR signaling. Inhibition of EGFR kinase blocks uPAR induced signal to ERK, implicating EGFR as an important effector of the pathway. Disruption of uPAR or EGFR signaling reduces HEp3 proliferation in vivo. These findings unveil a mechanism whereby uPAR subverts ligand-regulated EGFR signaling, providing cancer cells with proliferative advantage.

Original languageEnglish (US)
Pages (from-to)445-457
Number of pages13
JournalCancer Cell
Volume1
Issue number5
DOIs
StatePublished - Jun 2002
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

Fingerprint

Dive into the research topics of 'EGFR is a transducer of the urokinase receptor initiated signal that is required for in vivo growth of a human carcinoma'. Together they form a unique fingerprint.

Cite this