Ezrin regulates cell-cell and cell-matrix adhesion, a possible role with E-cadherin/beta-catenin

1999 ◽  
Vol 112 (18) ◽  
pp. 3081-3090 ◽  
Author(s):  
S. Hiscox ◽  
W.G. Jiang

Ezrin, radixin, moesin and merlin form a subfamily of conserved proteins in the band 4.1 superfamily. The function of these proteins is to link the plasma membrane to the actin cytoskeleton. Merlin is defective or absent in schwannomas and meningiomas and has been suggested to function as a tumour suppressor. In this study, we have examined the role of ezrin as a potential regulator of the adhesive and invasive behaviour of tumour cells. We have shown that following inhibition of ezrin expression in colo-rectal cancer cells using antisense oligonucleotides, these cells displayed a reduced cell-cell adhesiveness together with a gain in their motile and invasive behaviour. These cells also displayed increased spreading over matrix-coated surfaces. Immunofluorescence studies revealed that antisense-treated cells also displayed an increased staining of paxillin in areas representing focal adhesions. Furthermore, coprecipitation studies revealed an association of ezrin with E-cadherin and beta-catenin. Induction of the phosphorylation of ezrin by orthovanadate and hepatocyte growth factor/scatter factor resulted in changes similar to those seen with antisense treatment, together with a marked decrease in the association of ezrin with both beta-catenin and E-cadherin. It is concluded that ezrin regulates cell-cell and cell-matrix adhesion, by interacting with cell adhesion molecules E-cadherin and beta-catenin, and may thus play an important role in the control of adhesion and invasiveness of cancer cells.

2011 ◽  
Vol 21 (04) ◽  
pp. 719-743 ◽  
Author(s):  
MARK A. J. CHAPLAIN ◽  
MIROSŁAW LACHOWICZ ◽  
ZUZANNA SZYMAŃSKA ◽  
DARIUSZ WRZOSEK

The process of invasion of tissue by cancer cells is crucial for metastasis — the formation of secondary tumours — which is the main cause of mortality in patients with cancer. In the invasion process itself, adhesion, both cell–cell and cell–matrix, plays an extremely important role. In this paper, a mathematical model of cancer cell invasion of the extracellular matrix is developed by incorporating cell–cell adhesion as well as cell–matrix adhesion into the model. Considering the interactions between cancer cells, extracellular matrix and matrix degrading enzymes, the model consists of a system of reaction–diffusion partial integro–differential equations, with nonlocal (integral) terms describing the adhesive interactions between cancer cells and the host tissue, i.e. cell–cell adhesion and cell–matrix adhesion. Having formulated the model, we prove the existence and uniqueness of global in time classical solutions which are uniformly bounded. Then, using computational simulations, we investigate the effects of the relative importance of cell–cell adhesion and cell–matrix adhesion on the invasion process. In particular, we examine the roles of cell–cell adhesion and cell–matrix adhesion in generating heterogeneous spatio-temporal solutions. Finally, in the discussion section, concluding remarks are made and open problems are indicated.


2004 ◽  
Vol 15 (6) ◽  
pp. 2943-2953 ◽  
Author(s):  
Celeste M. Nelson ◽  
Dana M. Pirone ◽  
John L. Tan ◽  
Christopher S. Chen

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.


2017 ◽  
Vol 8 (1) ◽  
Author(s):  
Xiang Qin ◽  
Byung Ouk Park ◽  
Jiaying Liu ◽  
Bing Chen ◽  
Valerie Choesmel-Cadamuro ◽  
...  

2013 ◽  
Vol 63 (6) ◽  
pp. 561-569 ◽  
Author(s):  
Takuya Magome ◽  
Tsuyoshi Hattori ◽  
Manabu Taniguchi ◽  
Toshiko Ishikawa ◽  
Shingo Miyata ◽  
...  

2006 ◽  
Vol 16 (Supplement 1) ◽  
pp. S18-S19
Author(s):  
A. Winklmeier ◽  
R. Bauer ◽  
S. Arndt ◽  
A. Bosserhoff

2014 ◽  
Vol 13 (1) ◽  
pp. 138-148 ◽  
Author(s):  
Erica di Martino ◽  
Gavin Kelly ◽  
Jo-An Roulson ◽  
Margaret A. Knowles

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