![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Vol. 15, Issue 6, 2943-2953, June 2004
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Departments of Biomedical Engineering and Oncology, Johns Hopkins School of Medicine, Baltimore, Maryland 21205
Submitted October 17, 2003;
Revised March 22, 2004;
Accepted March 22, 2004
Monitoring Editor: Martin A. Schwartz
Changes in vascular endothelial (VE)-cadherin–mediated cell-cell adhesion and integrin-mediated cell-matrix adhesion coordinate to affect the physical and mechanical rearrangements of the endothelium, although the mechanisms for such cross talk remain undefined. Herein, we describe the regulation of focal adhesion formation and cytoskeletal tension by intercellular VE-cadherin engagement, and the molecular mechanism by which this occurs. Increasing the density of endothelial cells to increase cell-cell contact decreased focal adhesions by decreasing cell spreading. This contact inhibition of cell spreading was blocked by disrupting VE-cadherin engagement with an adenovirus encoding dominant negative VE-cadherin. When changes in cell spreading were prevented by culturing cells on a micropatterned substrate, VE-cadherin–mediated cell-cell contact paradoxically increased focal adhesion formation. We show that VE-cadherin engagement mediates each of these effects by inducing both a transient and sustained activation of RhoA. Both the increase and decrease in cell-matrix adhesion were blocked by disrupting intracellular tension and signaling through the Rho-ROCK pathway. In all, these findings demonstrate that VE-cadherin signals through RhoA and the actin cytoskeleton to cross talk with cell-matrix adhesion and thereby define a novel pathway by which cell-cell contact alters the global mechanical and functional state of cells.
Abbreviations used: EMT, epithelial-mesenchymal transition; FA, focal adhesion; ROCK, Rho kinase; VE-cadherin, vascular endothelial-cadherin.
Online version of this article contains supporting material. Online version is available at www.molbiolcell.org.
* Corresponding author. E-mail address: cchen{at}bme.jhu.edu.
This article has been cited by other articles:
|
|
 |
|
  H.-H. Lee and Z.-F. Chang Regulation of RhoA-dependent ROCKII activation by Shp2 J. Cell Biol., June 16, 2008; 181(6): 999 - 1012. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Rodewald, D. Herr, H.M. Fraser, G. Hack, R. Kreienberg, and C. Wulff Regulation of tight junction proteins occludin and claudin 5 in the primate ovary during the ovulatory cycle and after inhibition of vascular endothelial growth factor Mol. Hum. Reprod., November 1, 2007; 13(11): 781 - 789. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G.P. van Nieuw Amerongen, C.M.L. Beckers, I.D. Achekar, S. Zeeman, R.J.P. Musters, and V.W.M. van Hinsbergh Involvement of Rho Kinase in Endothelial Barrier Maintenance Arterioscler. Thromb. Vasc. Biol., November 1, 2007; 27(11): 2332 - 2339. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. F. Liu, C. M. Nelson, J. L. Tan, and C. S. Chen Cadherins, RhoA, and Rac1 Are Differentially Required for Stretch-Mediated Proliferation in Endothelial Versus Smooth Muscle Cells Circ. Res., August 31, 2007; 101(5): e44 - e52. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. L. Johansen and E. J. Brown Dual Regulation of SIRP{alpha} Phosphorylation by Integrins and CD47 J. Biol. Chem., August 17, 2007; 282(33): 24219 - 24230. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. J. Marshall Rho Family GTPase Signaling in Tumor Cell Movement and Angiogenesis Am. Assoc. Cancer Res. Educ. Book, April 14, 2007; 2007(1): 103 - 108. [Full Text] [PDF]
|
|
|
|
|
|
D. M. Pirone, W. F. Liu, S. A. Ruiz, L. Gao, S. Raghavan, C. A. Lemmon, L. H. Romer, and C. S. Chen An inhibitory role for FAK in regulating proliferation: a link between limited adhesion and RhoA-ROCK signaling J. Cell Biol., July 17, 2006; 174(2): 277 - 288. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Liebner, U. Cavallaro, and E. Dejana The Multiple Languages of Endothelial Cell-to-Cell Communication Arterioscler. Thromb. Vasc. Biol., July 1, 2006; 26(7): 1431 - 1438. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. F. Liu, C. M. Nelson, D. M. Pirone, and C. S. Chen E-cadherin engagement stimulates proliferation via Rac1 J. Cell Biol., May 8, 2006; 173(3): 431 - 441. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. E. Ingber Cellular mechanotransduction: putting all the pieces together again FASEB J, May 1, 2006; 20(7): 811 - 827. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Tzima Role of Small GTPases in Endothelial Cytoskeletal Dynamics and the Shear Stress Response Circ. Res., February 3, 2006; 98(2): 176 - 185. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. T. Fox, C. C. F. Homem, S. H. Myster, F. Wang, E. E. Bain, and M. Peifer Rho1 regulates Drosophila adherens junctions independently of p120ctn Development, November 1, 2005; 132(21): 4819 - 4831. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. E. Ingber Mechanical control of tissue growth: Function follows form PNAS, August 16, 2005; 102(33): 11571 - 11572. [Full Text] [PDF]
|
|
|
|
|
|
C. M. Nelson, R. P. Jean, J. L. Tan, W. F. Liu, N. J. Sniadecki, A. A. Spector, and C. S. Chen From the Cover: Emergent patterns of growth controlled by multicellular form and mechanics PNAS, August 16, 2005; 102(33): 11594 - 11599. [Abstract] [Full Text] [PDF]
|
|
