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Publication : Erk regulation of actin capping and bundling by Eps8 promotes cortex tension and leader bleb-based migration.

First Author  Logue JS Year  2015
Journal  Elife Volume  4
Pages  e08314 PubMed ID  26163656
Mgi Jnum  J:225986 Mgi Id  MGI:5695416
Doi  10.7554/eLife.08314 Citation  Logue JS, et al. (2015) Erk regulation of actin capping and bundling by Eps8 promotes cortex tension and leader bleb-based migration. Elife 4:e08314
abstractText  Within the confines of tissues, cancer cells can use blebs to migrate. Eps8 is an actin bundling and capping protein whose capping activity is inhibited by Erk, a key MAP kinase that is activated by oncogenic signaling. We tested the hypothesis that Eps8 acts as an Erk effector to modulate actin cortex mechanics and thereby mediate bleb-based migration of cancer cells. Cells confined in a non-adhesive environment migrate in the direction of a very large 'leader bleb.' Eps8 bundling activity promotes cortex tension and intracellular pressure to drive leader bleb formation. Eps8 capping and bundling activities act antagonistically to organize actin within leader blebs, and Erk mediates this effect. An Erk biosensor reveals concentrated kinase activity within leader blebs. Bleb contents are trapped by the narrow neck that separates the leader bleb from the cell body. Thus, Erk activity promotes actin bundling by Eps8 to enhance cortex tension and drive the bleb-based migration of cancer cells under non-adhesive confinement.
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