Article

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

Department of Internal Medicine I, University of Ulm, Ulm, Baden-Wuerttemberg, Germany.
Oncogene (impact factor: 6.37). 03/2010; 29(18):2724-38. DOI:10.1038/onc.2010.25 pp.2724-38
Source: PubMed

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.

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Keywords

cell behavior
 
cellular contractility
 
cellular forces influence cancer-cell behavior
 
chorioallantoic membrane
 
collagen-coated beads
 
forces
 
human SW480 colon cancer cells sets
 
independent
 
key elements
 
low-rigidity surfaces
 
matrix forces
 
Microenvironmental clues
 
myosin light chain kinase
 
potential targets
 
receptor-type tyrosine-protein phosphatase alpha
 
responses
 
RPTPalpha
 
RPTPalpha influences
 
RPTPalpha-mediated increase
 
stress fibers