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

被引：85
作者：
Logue, Jeremy S. [1 ,2 ]
Cartagena-Rivera, Alexander X. [2 ]
Baird, Michelle A. [1 ]
Davidson, Michael W. [3 ,4 ]
Chadwick, Richard S. [2 ]
Waterman, Clare M. [1 ]
机构：
[1] NHLBI, NIH, Bethesda, MD 20892 USA
[2] NIDCD, NIH, Bethesda, MD USA
[3] Florida State Univ, Natl High Magnet Field Lab, Tallahassee, FL 32306 USA
[4] Florida State Univ, Dept Biol Sci, B-157, Tallahassee, FL 32306 USA
来源：
ELIFE | 2015年 / 4卷
关键词：
ACTIVATED PROTEIN-KINASE; CELL-MIGRATION; CANCER-THERAPY; MYOSIN-II; ADHESION; MOTILITY; GROWTH; GENE; MORPHOGENESIS; LAMELLIPODIA;
D O I：
10.7554/eLife.08314
中图分类号：
Q [生物科学];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
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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页数：31
相关论文
共 51 条
[11]   Regulation of cell shape by Cdc42 is mediated by the synergic actin-bundling activity of the Eps8-IRSp53 complex [J].
Disanza, Andrea ;
Mantoani, Sara ;
Hertzog, Maud ;
Gerboth, Silke ;
Frittoli, Emanuela ;
Steffen, Anika ;
Berhoerster, Kerstin ;
Kreienkamp, Hans-Juergen ;
Milanesi, Francesca ;
Di Fiore, Pier Paolo ;
Ciliberto, Andrea ;
Stradal, Theresia E. B. ;
Scita, Giorgio .
NATURE CELL BIOLOGY, 2006, 8 (12) :1337-U15
[12]   Targeting ras signalling pathways in cancer therapy [J].
Downward, J .
NATURE REVIEWS CANCER, 2003, 3 (01) :11-22
[13]   Moesin orchestrates cortical polarity of melanoma tumour cells to initiate 3D invasion [J].
Estecha, Ana ;
Sanchez-Martin, Lorena ;
Puig-Kroeger, Amaya ;
Bartolome, Ruben A. ;
Teixido, Joaquin ;
Samaniego, Rafael ;
Sanchez-Mateos, Paloma .
JOURNAL OF CELL SCIENCE, 2009, 122 (19) :3492-3501
[14]   EPS8, A SUBSTRATE FOR THE EPIDERMAL GROWTH-FACTOR RECEPTOR KINASE, ENHANCES EGF-DEPENDENT MITOGENIC SIGNALS [J].
FAZIOLI, F ;
MINICHIELLO, L ;
MATOSKA, V ;
CASTAGNINO, P ;
MIKI, T ;
WONG, WT ;
DIFIORE, PP .
EMBO JOURNAL, 1993, 12 (10) :3799-3808
[15]   Quantification of surface tension and internal pressure generated by single mitotic cells [J].
Fischer-Friedrich, Elisabeth ;
Hyman, Anthony A. ;
Juelicher, Frank ;
Mueller, Daniel J. ;
Helenius, Jonne .
SCIENTIFIC REPORTS, 2014, 4
[16]   Meta-analysis and meta-review of thyroid cancer gene expression profiling studies identifies important diagnostic biomarkers [J].
Griffith, Obi L. ;
Melck, Adrienne ;
Jones, Steven J. M. ;
Wiseman, Sam M. .
JOURNAL OF CLINICAL ONCOLOGY, 2006, 24 (31) :5043-5051
[17]   A genetically encoded fluorescent sensor of ERK activity [J].
Harvey, Christopher D. ;
Ehrhardt, Anka G. ;
Cellurale, Cristina ;
Zhong, Haining ;
Yasuda, Ryohei ;
Davis, Roger J. ;
Svoboda, Karel .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2008, 105 (49) :19264-19269
[18]   Molecular Basis for the Dual Function of Eps8 on Actin Dynamics: Bundling and Capping [J].
Hertzog, Maud ;
Milanesi, Francesca ;
Hazelwood, Larnele ;
Disanza, Andrea ;
Liu, HongJun ;
Perlade, Emilie ;
Malabarba, Maria Grazia ;
Pasqualato, Sebastiano ;
Maiolica, Alessio ;
Confalonieri, Stefano ;
Le Clainche, Christophe ;
Offenhauser, Nina ;
Block, Jennifer ;
Rottner, Klemens ;
Di Fiore, Pier Paolo ;
Carlier, Marie-France ;
Volkmann, Niels ;
Hanein, Dorit ;
Scita, Giorgio .
PLOS BIOLOGY, 2010, 8 (06)
[19]   CALIBRATION OF ATOMIC-FORCE MICROSCOPE TIPS (VOL 64, PG 1868, 1993) [J].
HUTTER, JL ;
BECHHOEFER, J .
REVIEW OF SCIENTIFIC INSTRUMENTS, 1993, 64 (11) :3342-3342
[20]  
JAIN RK, 1987, CANCER RES, V47, P3039
123456