Research ArticleCell Biology

PKCɛ Regulation of an α5 Integrin–ZO-1 Complex Controls Lamellae Formation in Migrating Cancer Cells

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Science Signaling  30 Jun 2009:
Vol. 2, Issue 77, pp. ra32
DOI: 10.1126/scisignal.2000135

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From Adhesions to Lamellae

The tight junction protein ZO-1 (zonula occludens-1) is involved in cell-cell adhesion, whereas integrins containing the α5 integrin subunit mediate both cell-cell and cell-matrix adhesion. Alterations in the abundance of ZO-1 and α5 are correlated with increased invasiveness in lung cancer cells. Through biochemical, RNA interference, and imaging techniques, Tuomi et al. found that ZO-1 and α5 interacted at the leading edge of migrating lung cancer cells, where the complex promoted lamellae formation and motility. Protein kinase Cɛ (PKCɛ) promoted the phosphorylation of ZO-1 at Ser168, which triggered the relocalization of ZO-1 from tight junctions to lamellae. The ZO-1–α5 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 α5 integrin may be involved in motility and invasion in vivo.