Focal adhesion kinase mediates defects in the force-dependent reinforcement of initial integrin-cytoskeleton linkages in metastatic colon cancer cell lines

Götz von Wichert, Denis Krndija, Heidrun Schmid, Georg von Wichert, Georg Haerter, Guido Adler, Thomas Seufferlein, Michael Sheetz

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Micro-environmental clues, including the biophysical interpretation of the extracellular matrix, are critical to proliferation, apoptosis and migration. Here, we show that metastatic human colon cancer cell lines display altered matrix interaction. Interaction of colon cancer cells with collagen I depends on integrins (mainly α11) but metastatic cells display delayed spreading and reduced extension of lamellipodia. In addition, cells show defective strengthening of integrin-cytoskeleton linkages upon mechanical stimulation, as determined by laser trapping experiments and binding of large beads to the cell surface. However, adhesion to pliable surfaces is ameliorated in metastatic variants. These changes are caused by constitutive activation of focal adhesion kinase (FAK) and can be modulated by changing expression and/or activity of FAK via RNA-interference or expression of inhibitory constructs, respectively. In addition, consistent with defective strengthening of integrin-cytoskeleton linkages, metastatic cell lines show reduced random motility. Taken together these data suggest that constitutive activation of FAK causes defects in spreading, reinforcement of integrin-cytoskeleton linkages and migration and at the same time could ameliorate the adhesion of metastatic cells to suboptimal surfaces.

Original languageEnglish (US)
Pages (from-to)1-16
Number of pages16
JournalEuropean Journal of Cell Biology
Volume87
Issue number1
DOIs
StatePublished - Jan 15 2008
Externally publishedYes

Keywords

  • Colon cancer
  • FAK
  • Focal contact
  • Force
  • Spreading

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology
  • Cell Biology

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