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Sci. Signal., 30 June 2009
Vol. 2, Issue 77, p. ra32
[DOI: 10.1126/scisignal.2000135]


Editor's Summary

From Adhesions to Lamellae
The tight junction protein ZO-1 (zonula occludens-1) is involved in cell-cell adhesion, whereas integrins containing the {alpha}5 integrin subunit mediate both cell-cell and cell-matrix adhesion. Alterations in the abundance of ZO-1 and {alpha}5 are correlated with increased invasiveness in lung cancer cells. Through biochemical, RNA interference, and imaging techniques, Tuomi et al. found that ZO-1 and {alpha}5 interacted at the leading edge of migrating lung cancer cells, where the complex promoted lamellae formation and motility. Protein kinase C{varepsilon} (PKC{varepsilon}) promoted the phosphorylation of ZO-1 at Ser168, which triggered the relocalization of ZO-1 from tight junctions to lamellae. The ZO-1–{alpha}5 complex was detected only in migrating cells in vitro and, intriguingly, was also present only in a subset of cells in metastatic lung tumors, suggesting that ZO-1 and {alpha}5 integrin may be involved in motility and invasion in vivo.

Citation: S. Tuomi, A. Mai, J. Nevo, J. O. Laine, V. Vilkki, T. J. Öhman, C. G. Gahmberg, P. J. Parker, J. Ivaska, PKC{varepsilon} Regulation of an {alpha}5 Integrin–ZO-1 Complex Controls Lamellae Formation in Migrating Cancer Cells. Sci. Signal. 2, ra32 (2009).

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