The E-cadherin cell–cell adhesion complex and lung cancer invasion, metastasis, and prognosis

Members of the SAP family of synapse-associated proteins have recently emerged as central players in the molecular organization of synapses. In this study, we have examined the mechanism that localizes one member, SAP97, to sites of cell-cell contact. Utilizing epithelial CACO-2 cells and fibroblast L-cells as model systems, we demonstrate that SAP97 is associated with the submembranous cortical cytoskeleton at cell-cell adhesion sites. Furthermore, we show that its localization into this structure is triggered by E-cadherin. Although SAP97 can be found in an E-cadherin/catenin adhesion complex, this interaction seems to be mediated by the attachment of SAP97 to the cortical cytoskeleton. Our results are consistent with a model in which SAP97 is recruited to sites of cell-cell contact via an E-cadherin induced assembly of the cortical cytoskeleton.

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Interaction of alpha-actinin with the cadherin/catenin cell-cell adhesion complex via alpha-catenin.

The Journal of Cell Biology ◽

10.1083/jcb.130.1.67 ◽

1995 ◽

Vol 130 (1) ◽

pp. 67-77 ◽

Cited By ~ 445

Author(s):

K A Knudsen ◽

A P Soler ◽

K R Johnson ◽

M J Wheelock

Keyword(s):

Cell Adhesion ◽

Cytoskeletal Proteins ◽

Beta Catenin ◽

Independent Manner ◽

Intracellular Proteins ◽

Direct Association ◽

Dependent Cell ◽

Adhesion Complex ◽

E Cadherin ◽

Cell Cell

Cadherins are Ca(2+)-dependent, cell surface glycoproteins involved in cell-cell adhesion. Extracellularly, transmembrane cadherins such as E-, P-, and N-cadherin self-associate, while intracellularly they interact indirectly with the actin-based cytoskeleton. Several intracellular proteins termed catenins, including alpha-catenin, beta-catenin, and plakoglobin, are tightly associated with these cadherins and serve to link them to the cytoskeleton. Here, we present evidence that in fibroblasts alpha-actinin, but not vinculin, colocalizes extensively with the N-cadherin/catenin complex. This is in contrast to epithelial cells where both cytoskeletal proteins colocalize extensively with E-cadherin and catenins. We further show that alpha-actinin, but not vinculin, coimmunoprecipitates specifically with alpha- and beta-catenin from N- and E-cadherin-expressing cells, but only if alpha-catenin is present. Moreover, we show that alpha-actinin coimmunoprecipitates with the N-cadherin/catenin complex in an actin-independent manner. We therefore propose that cadherin/catenin complexes are linked to the actin cytoskeleton via a direct association between alpha-actinin and alpha-catenin.

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αE-catenin regulates actin dynamics independently of cadherin-mediated cell–cell adhesion

The Journal of Cell Biology ◽

10.1083/jcb.200910041 ◽

2010 ◽

Vol 189 (2) ◽

pp. 339-352 ◽

Cited By ~ 111

Author(s):

Jacqueline M. Benjamin ◽

Adam V. Kwiatkowski ◽

Changsong Yang ◽

Farida Korobova ◽

Sabine Pokutta ◽

...

Keyword(s):

Cell Adhesion ◽

Actin Polymerization ◽

Membrane Dynamics ◽

Actin Dynamics ◽

Filamentous Actin ◽

Vitro Binding ◽

Adhesion Complex ◽

E Cadherin ◽

Cell Cell

αE-catenin binds the cell–cell adhesion complex of E-cadherin and β-catenin (β-cat) and regulates filamentous actin (F-actin) dynamics. In vitro, binding of αE-catenin to the E-cadherin–β-cat complex lowers αE-catenin affinity for F-actin, and αE-catenin alone can bind F-actin and inhibit Arp2/3 complex–mediated actin polymerization. In cells, to test whether αE-catenin regulates actin dynamics independently of the cadherin complex, the cytosolic αE-catenin pool was sequestered to mitochondria without affecting overall levels of αE-catenin or the cadherin–catenin complex. Sequestering cytosolic αE-catenin to mitochondria alters lamellipodia architecture and increases membrane dynamics and cell migration without affecting cell–cell adhesion. In contrast, sequestration of cytosolic αE-catenin to the plasma membrane reduces membrane dynamics. These results demonstrate that the cytosolic pool of αE-catenin regulates actin dynamics independently of cell–cell adhesion.

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E-cadherin-catenin cell-cell adhesion complex and human cancer

British Journal of Surgery ◽

10.1046/j.1365-2168.2000.01513.x ◽

2000 ◽

Vol 87 (8) ◽

pp. 992-1005 ◽

Cited By ~ 283

Author(s):

B. P. L. Wijnhoven ◽

W. N. M. Dinjens ◽

M. Pignatelli

Keyword(s):

Cell Adhesion ◽

Human Cancer ◽

Adhesion Complex ◽

E Cadherin ◽

Cell Cell

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622: Von Hippel-Lindau Inactivation Downregulates the Cell-Cell Adhesion Molecule E Cadherin in Renal Cancer Cells

The Journal of Urology ◽

10.1016/s0022-5347(18)34862-6 ◽

2005 ◽

Vol 173 (4S) ◽

pp. 170-170

Author(s):

Maxine G. Tran ◽

Miguel A. Esteban ◽

Peter D. Hill ◽

Ashish Chandra ◽

Tim S. O'Brien ◽

...

Keyword(s):

Cell Adhesion ◽

Cancer Cells ◽

Renal Cancer ◽

Adhesion Molecule ◽

Cell Adhesion Molecule ◽

Von Hippel Lindau ◽

E Cadherin ◽

Cell Cell

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Faculty Opinions recommendation of cis-Dimer formation of E-cadherin is independent of cell-cell adhesion assembly in vivo.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1018391.209464 ◽

2004 ◽

Author(s):

Deborah Leckband

Keyword(s):

Cell Adhesion ◽

Dimer Formation ◽

E Cadherin ◽

Cell Cell

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Keratin 19 maintains E-cadherin localization at the cell surface and stabilizes cell-cell adhesion of MCF7 cells

Cell Adhesion & Migration ◽

10.1080/19336918.2020.1868694 ◽

2021 ◽

Vol 15 (1) ◽

pp. 1-17

Author(s):

Sarah Alsharif ◽

Pooja Sharma ◽

Karina Bursch ◽

Rachel Milliken ◽

Van Lam ◽

...

Keyword(s):

Cell Adhesion ◽

Cell Surface ◽

Mcf7 Cells ◽

Keratin 19 ◽

E Cadherin ◽

Cell Cell

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Changes in E-cadherin rigidity sensing regulate cell adhesion

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1618676114 ◽

2017 ◽

Vol 114 (29) ◽

pp. E5835-E5844 ◽

Cited By ~ 34

Author(s):

Caitlin Collins ◽

Aleksandra K. Denisin ◽

Beth L. Pruitt ◽

W. James Nelson

Keyword(s):

Cell Adhesion ◽

Signaling Molecules ◽

Membrane Dynamics ◽

Cell Contact ◽

Adhesion Assay ◽

Cell Periphery ◽

Actin Organization ◽

Rigidity Sensing ◽

E Cadherin ◽

Cell Cell

Mechanical cues are sensed and transduced by cell adhesion complexes to regulate diverse cell behaviors. Extracellular matrix (ECM) rigidity sensing by integrin adhesions has been well studied, but rigidity sensing by cadherins during cell adhesion is largely unexplored. Using mechanically tunable polyacrylamide (PA) gels functionalized with the extracellular domain of E-cadherin (Ecad-Fc), we showed that E-cadherin–dependent epithelial cell adhesion was sensitive to changes in PA gel elastic modulus that produced striking differences in cell morphology, actin organization, and membrane dynamics. Traction force microscopy (TFM) revealed that cells produced the greatest tractions at the cell periphery, where distinct types of actin-based membrane protrusions formed. Cells responded to substrate rigidity by reorganizing the distribution and size of high-traction-stress regions at the cell periphery. Differences in adhesion and protrusion dynamics were mediated by balancing the activities of specific signaling molecules. Cell adhesion to a 30-kPa Ecad-Fc PA gel required Cdc42- and formin-dependent filopodia formation, whereas adhesion to a 60-kPa Ecad-Fc PA gel induced Arp2/3-dependent lamellipodial protrusions. A quantitative 3D cell–cell adhesion assay and live cell imaging of cell–cell contact formation revealed that inhibition of Cdc42, formin, and Arp2/3 activities blocked the initiation, but not the maintenance of established cell–cell adhesions. These results indicate that the same signaling molecules activated by E-cadherin rigidity sensing on PA gels contribute to actin organization and membrane dynamics during cell–cell adhesion. We hypothesize that a transition in the stiffness of E-cadherin homotypic interactions regulates actin and membrane dynamics during initial stages of cell–cell adhesion.

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