Gangliosides inhibit urokinase-type plasminogen activator (uPA)-dependent squamous carcinoma cell migration by preventing uPA receptor/α 5β1 integrin/epidermal growth factor receptor interactions

Xiao Qi Wang*, Ping Sun, Amy S. Paller

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

Abstract

The interaction of the urokinase-type plasminogen activator (uPA) receptor (uPAR) with integrins plays a critical role in the regulation of cell adhesion and migration. However, the molecular events underlying the modulation of the interaction of uPAR and integrin are poorly understood. Gangliosides are thought to regulate epithelial cell adhesion and migration by inhibiting α5β1 integrin and epidermal growth factor receptor (EGFR) signaling. We report here that increases in the expression of ganglioside NeuAcα2 → 3Galβ1 → 3GalNAcβ1 → 4(NeuAcα2 → 8NeuAcα2 → 3)Galβ1 → 4Glcβ1-Cer (GT1b) or NeuAcα2 → 3Galβ1 - 4Glcβ1-Cer (GM3) inhibit uPA-dependent cell migration by preventing the association of uPAR with α5β1 integrin or uPAR/α5β 1 integrin with the EGFR, respectively. As a result, uPA-dependent focal adhesion kinase (FAK) and integrin-mediated EGFR signaling are suppressed. Both gangliosides inhibit uPAR signaling-stimulated migration; however, GM3 inhibits uPA-induced EGFR phosphorylation by blocking the crosstalk between integrin and EGFR, whereas GT1b suppresses both uPA-induced FAK and EGFR activation by preventing the activation of integrin α5β 1.

Original languageEnglish (US)
Pages (from-to)839-848
Number of pages10
JournalJournal of Investigative Dermatology
Volume124
Issue number4
DOIs
StatePublished - Apr 2005

Keywords

  • Antisense
  • FAK
  • GPI
  • PPPP
  • Sialidase

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

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