Blocking the integrin that controls unidirectional migration activated a pathway via Akt kinase, says study in Journal of Cell Biology.

A team of researchers report how the changed behavior of integrins can prompt metastatic movement in tumor cells.  Blocking a particular integrin, initiated a proinvasive pathway headed by the Akt kinase, which increased the cells’ invasive capability.

Recent research has suggested that an integrin called a5b1 drives random cellular movement, while an integrin called avb3 has been associated with unidirectional migration. The balance of the two actions determines final movement.

To discover the contribution of a5b1 to random migration, investigators blocked avb3. The treated cells changed their mode of migration from unidirectional to random and displayed an increase in their ability to invade 3-D gels. The changed behavior correlated with an increase in trafficking of a5b1 from intracellular compartments to anterior membrane protrusions.

This increased trafficking, however, did not significantly alter a5b1’s contribution to cell adhesion. The ease with which cells were dislodged from a spinning disk increased as the amount of avb3 was reduced but was not correlated with any change in a5b1.

This meant that the cells’ increased invasive ability was due to alteration in some other property, which turned out to be the triggering of a pathway headed by the Akt kinase, the scientists explain. In avb3-blocked cells, a5b1 became associated with epidermal growth factor receptor 1 (EGFR1), which in turn increased EGFR1’s autophosphorylation and abundance at membrane protrusions, and EGFR1 is a known activator of the Akt pathway.

This research appears in the October 6 edition of Journal of Cell Biology. The study was a collaboration of researchers from the Beatson Institute for Cancer Research in Glasgow, the University of Pennsylvania, and the University College Cork, Ireland.

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