Focal adhesion kinase (FAK) phosphorylation is not required for genistein-induced FAK-β-1-integrin complex formation

Yueqin Liu, Edward Kyle, Ronald Lieberman, James Crowell, Gary Kelloff, Raymond C. Bergan

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

It has previously been shown that changes in the activity of focal adhesion kinase (FAK), and its binding to β-1-integrin, accompany genistein-induced adhesion of prostate cells. Consumption of genistein world wide is associated with a lower incidence of metastatic prostate cancer. Early human clinical trials of genistein are under way to evaluate genistein's potential causal role in this regard. Though an important cell adhesion-associated signaling molecule, FAK's role in regulating prostate cell adhesion was not clear. Elucidation of this process would provide important information relating to both biology and potential clinical endpoints. It was hypothesized that FAK activation and complex formation are temporally related in prostate cells, and can thus be separated. Significant activation of FAK was demonstrated when cells adhered to fibronectin, as compared to poly-L-lysine, thus demonstrating that β-1-integrin plays a significant role in activating FAK. Neither FAK activation, nor FAK-integrin complex formation, required β-1-integrin ligand. However, disruption of the cellular cytoskeleton by cytochalasin D prevented FAK activation, but did not block genistein-induced complex formation. In the face of a disrupted cytoskeleton, signaling through FAK could not be restored through either integrin cross linking, or re-establishment of tensile forces via attachment to solid matrix. These studies demonstrate that FAK-β-1-integrin complex formation does not require FAK activation, suggesting that it is an early event in prostate cell adhesion. An intact cytoskeleton is necessary for FAK activation. The functional importance of β-1-integrin in prostate cells is demonstrated. Current findings support plans to test genistein in prostate cancer.

Original languageEnglish (US)
Article number314850
Pages (from-to)203-212
Number of pages10
JournalClinical and Experimental Metastasis
Volume18
Issue number3
DOIs
StatePublished - Jan 1 2000

Keywords

  • Cell adhesion
  • Focal adhesion kinase
  • Genistein
  • Integrin
  • Prostate cancer
  • Tyrosine kinase inhibitor

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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