Substrate stiffness and the receptor-type tyrosine-protein phosphatase alpha regulate spreading of colon cancer cells through cytoskeletal contractility

Oncogene. 2010 May 6;29(18):2724-38. doi: 10.1038/onc.2010.25. Epub 2010 Mar 8.

Abstract

Microenvironmental clues are critical to cell behavior. One of the key elements of migration is the generation and response to forces. Up to now, there is no definitive concept on how the generation and responses to cellular forces influence cancer-cell behavior. Here, we show that expression of receptor-type tyrosine-protein phosphatase alpha (RPTPalpha) in human SW480 colon cancer cells sets a threshold for the response to matrix forces by changing cellular contractility. This can be explained as an RPTPalpha-mediated increase in contractility with a consecutive increase in number and size of adhesion sites and stress fibers. These effects are mediated through myosin light chain kinase and largely independent of Rho/Rho-kinase (ROCK) signaling. In addition, we report that RPTPalpha influences spreading on low-rigidity surfaces, binding of collagen-coated beads and expression of RPTPalpha is required for invasion into the chorioallantoic membrane. These data suggest that force-responsive proteins such as RPTPalpha can influence cancer-cell behavior and identify potential targets for cancer therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Adhesion
  • Cell Line, Tumor
  • Colonic Neoplasms / pathology*
  • Cytoskeleton / physiology*
  • Elasticity
  • Humans
  • Muscle Contraction
  • Myosin-Light-Chain Kinase / physiology
  • Neoplasm Invasiveness
  • Receptor-Like Protein Tyrosine Phosphatases, Class 4 / physiology*
  • rho-Associated Kinases / physiology
  • src-Family Kinases / physiology

Substances

  • src-Family Kinases
  • rho-Associated Kinases
  • Myosin-Light-Chain Kinase
  • PTPRA protein, human
  • Receptor-Like Protein Tyrosine Phosphatases, Class 4