Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text (PDF, 906K) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Robinson, R. Search for Related Content PubMed Articles by Robinson, R. Social Bookmarking                            What's this?

Random, fast, and out of control

An increase in 5β1 recycling promotes extension of long pseudopods at the cell front (arrow shows direction) in a 3D matrix.

Caswell et al. report how the altered behavior of integrins can prompt metastatic movement in tumor cells.

On 2D surfaces, cells may migrate randomly, or be strongly unidirectional. Integrins, which link the cell to the extracellular matrix, are known to influence the mode of migration, but exactly how has been unclear. Recent work has suggested that an integrin called 5β1 drives random movement, while an integrin called vβ3 has been associated with unidirectional migration—the balance of activity between the two determining the type of movement. To further explore the contribution of 5β1 to random migration, the authors thus blocked vβ3.

The treated cells changed their mode of migration from unidirectional to random, and their ability to invade 3D gels increased. The changed behavior correlated with an increase in trafficking of 5β1 from intracellular compartments to anterior membrane protrusions. But this increase in trafficking did not significantly alter 5β1's contribution to cell adhesion—the ease with which cells were dislodged from a spinning disk increased as the amount of vβ3 was reduced, but was not correlated with any change in 5β1. This suggested that the cells' increased invasive ability was due to alteration in some other property. That property turned out to be activation of a proinvasive pathway headed by a kinase called Akt.

In vβ3-blocked cells, 5β1 became associated with epidermal growth factor receptor 1 (EGFR1), which increased EGFR1's abundance at the membrane protrusions, as well as its autophosphorylation. Because EGFR1 is an activator of the Akt pathway, hey presto, the cells took on some new moves.

Caswell, P.T., et al. 2008. J. Cell Biol. doi:10.1083/jcb.200804140.[Abstract/Free Full Text]

Richard Robinson

rrobinson{at}nasw.org

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This Article Full Text (PDF, 906K) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Robinson, R. Search for Related Content PubMed Articles by Robinson, R. Social Bookmarking                            What's this?