title: Erk regulation of actin capping and bundling by Eps8 promotes cortex tension and leader bleb-based migration.
abstract: 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.
authors.affiliation: National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, United States.
authors.forename: Jeremy S
authors.initials: JS
authors.lastname: Logue
authors.affiliation: National Institute on Deafness and other Communication Disorders, National Institutes of Health, Bethesda, United States.
authors.forename: Alexander X
authors.initials: AX
authors.lastname: Cartagena-Rivera
authors.affiliation: National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, United States.
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Baird
authors.affiliation: National High Magnetic Field Laboratory and Department of Biological Science, Florida State University, Tallahassee, United States.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Davidson
authors.affiliation: National Institute on Deafness and other Communication Disorders, National Institutes of Health, Bethesda, United States.
authors.forename: Richard S
authors.initials: RS
authors.lastname: Chadwick
authors.affiliation: National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, United States.
authors.forename: Clare M
authors.initials: CM
authors.lastname: Waterman
mesh_terms: D000199:Actins / Q000378:metabolism*; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006801:Humans
chemical_list: D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; C489989:EPS8 protein, human; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: Eps8; Erk; actin; adhesion-independent cell migration; bleb; cancer cell biology; cell biology; human