Sci. Signal., 30 June 2009
From Adhesions to LamellaeThe tight junction protein ZO-1 (zonula occludens-1) is involved in cell-cell adhesion, whereas integrins containing the 5 integrin subunit mediate both cell-cell and cell-matrix adhesion. Alterations in the abundance of ZO-1 and 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 5 interacted at the leading edge of migrating lung cancer cells, where the complex promoted lamellae formation and motility. Protein kinase C (PKC) promoted the phosphorylation of ZO-1 at Ser168, which triggered the relocalization of ZO-1 from tight junctions to lamellae. The ZO-1–5 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 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 Regulation of an 5 Integrin–ZO-1 Complex Controls Lamellae Formation in Migrating Cancer Cells. Sci. Signal. 2, ra32 (2009).
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