rock1 and limk2 interact in spread but not blebbing cancer cellsrock1和limk2互动传播但不起泡癌细胞.pdfVIP

ROCK1 and LIMK2 Interact in Spread but Not Blebbing Cancer Cells 1,2 1,3 2 1 Kerry F. Shea , Claire M. Wells , Andrew P. Garner , Gareth E. Jones * 1 Randall Division of Cell Molecular Biophysics, King’s College London, London, United Kingdom, 2 AstraZeneca, Cancer and Infection Research Area, Macclesfield, United Kingdom, 3 Division of Cancer Studies, Kings College London, London, United Kingdom Abstract Cancer cells migrating within a 3D microenvironment are able to adopt either a mesenchymal or amoeboid mode of migration. Amoeboid migration is characterised by membrane blebbing that is dependent on the Rho effectors, ROCK1/2. We identify LIMK2 as the preferred substrate for ROCK1 but find that LIMK2 did not induce membrane blebbing, suggesting that a LIMK2 pathway is not involved in amoeboid-mode migration. In support of this hypothesis, novel FRET data demonstrate a direct interaction between ROCK1 and LIMK2 in polarised but not blebbing cells. Our results point to a specific role for the ROCK1:LIMK2 pathway in mesenchymal-mode migration. Citation: Shea KF, Wells CM, Garner AP, Jones GE (2008) ROCK1 and LIMK2 Interact in Spread but Not Blebbing Cancer Cells. PLoS ONE 3(10): e3398. doi:10.1371/ journal.pone.0003398 Editor: Carl-Philipp Heisenberg, Max Planck Institute of Molecular Cell Biology and Genetics, Germany Received July 8, 2008; Accepted September 16, 2008; Published October 14, 2008 Copyright: 2008 Shea et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This work was sup