MMP proteolytic activity regulates cancer invasiveness by modulating integrins

Sci Rep. 2017 Oct 27;7(1):14219. doi: 10.1038/s41598-017-14340-w.

Abstract

Cancer invasion through dense extracellular matrices (ECMs) is mediated by matrix metalloproteinases (MMPs) which degrade the ECM thereby creating paths for migration. However, how this degradation influences the phenotype of cancer cells is not fully clear. Here we address this question by probing the function of MMPs in regulating biophysical properties of cancer cells relevant to invasion. We show that MMP catalytic activity regulates cell spreading, motility, contractility and cortical stiffness by stabilizing integrins at the membrane and activating focal adhesion kinase. Interestingly, cell rounding and cell softening on stiff gels induced by MMP inhibition is attenuated on MMP pre-conditioned surfaces. Together, our results suggest that MMP catalytic activity regulates invasiveness of cancer cells by modulating integrins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomechanical Phenomena
  • Cell Adhesion
  • Cell Line, Tumor
  • Cell Membrane / metabolism
  • Cell Movement
  • Extracellular Matrix / metabolism
  • Humans
  • Integrin beta1 / metabolism
  • Integrins / metabolism*
  • Matrix Metalloproteinases / metabolism*
  • Neoplasm Invasiveness
  • Protein Transport
  • Proteolysis*

Substances

  • Integrin beta1
  • Integrins
  • Matrix Metalloproteinases