Cross-talk of integrin α3β1 and tissue factor in cell migration

Andrea Dorfleutner, Edith Hintermann, Takehiko Tarui, Yoshikazu Takada, Wolfram Ruf

Research output: Contribution to journalArticle

121 Citations (Scopus)

Abstract

In cancer and angiogenesis, coagulation-independent roles of tissue factor (TF) in cell migration are incompletely understood. Immobilized anti-TF extracellular domain antibodies induce cell spreading, but this phenomenon is epitope specific and is not induced by anti-TF 5G9. Spreading on anti-TF is β1 integrin-dependent, indicating functional interactions of the TF extracellular domain 5G9 epitope (a presumed integrin-binding site) and integrins. Recombinant TF extracellular domain supports adhesion of cells expressing αvβ3 or certain β1 integrin heterodimers (α3β1, α4β1, α5β1, α6β1, α9β1) and adhesion is blocked by specific anti-integrin antibodies or mutations in the integrin ligand-binding site. Although several studies have linked TF to cell migration, we here demonstrate that TF specifically regulates α3β1-dependent migration on laminin 5. Expression of TF suppresses α3β1-dependent migration, but only when the TF cytoplasmic domain is not phosphorylated. Suppression of migration can be reversed by 5G9, presumably by disrupting integrin interaction, or by the protease ligand VIIa, known to induce PAR-2-dependent phosphorylation of TF. In both cases, release of α3β1 inhibition is prevented by mutation of critical phosphorylation sites in the TF cytoplasmic domain. Thus, TF influences integrin-mediated migration through cooperative intra- and extracellular interactions and phosphorylation regulates TF's function in cell motility.

Original languageEnglish
Pages (from-to)4416-4425
Number of pages10
JournalMolecular Biology of the Cell
Volume15
Issue number10
DOIs
Publication statusPublished - Oct 2004

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Dorfleutner, A., Hintermann, E., Tarui, T., Takada, Y., & Ruf, W. (2004). Cross-talk of integrin α3β1 and tissue factor in cell migration. Molecular Biology of the Cell, 15(10), 4416-4425. https://doi.org/10.1091/mbc.E03-09-0640