Matrix rigidity activates wnt signaling through down-regulation of dickkopf-1 protein

Maria V. Barbolina, Yiuying Liu, Hilal Gurler, Mijung Kim, Andre A. Kajdacsy-Balla, Lisa Rooper, Jaclyn Shepard, Michael Weiss, Lonnie D. Shea, Peter Penzes, Matthew J. Ravosa, M. Sharon Stack

Research output: Contribution to journalArticlepeer-review

Abstract

Cells respond to changes in the physical properties of the extracellular matrix with altered behavior and gene expression, highlighting the important role of the microenvironment in the regulation of cell function. In the current study, culture of epithelial ovarian cancer cells on three-dimensional collagen I gels led to a dramatic down-regulation of the Wnt signaling inhibitor dickkopf-1 with a concomitant increase in nuclear β-catenin and enhanced β-catenin/Tcf/Lef transcriptional activity. Increased three-dimensional collagen gel invasion was accompanied by transcriptional up-regulation of the membrane-tethered collagenase membrane type 1 matrix metalloproteinase, and an inverse relationship between dickkopf-1 and membrane type 1 matrix metalloproteinase was observed in human epithelial ovarian cancer specimens. Similar results were obtained in other tissue-invasive cells such as vascular endothelial cells, suggesting a novel mechanism for functional coupling of matrix adhesion with Wnt signaling.

Original languageEnglish (US)
Pages (from-to)141-151
Number of pages11
JournalJournal of Biological Chemistry
Volume288
Issue number1
DOIs
StatePublished - Jan 4 2013
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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