scholarly journals Dynamic and Static Interactions between p120 Catenin and E-Cadherin Regulate the Stability of Cell-Cell Adhesion

Cell ◽  
2010 ◽  
Vol 141 (1) ◽  
pp. 117-128 ◽  
Author(s):  
Noboru Ishiyama ◽  
Seung-Hye Lee ◽  
Shuang Liu ◽  
Guang-Yao Li ◽  
Matthew J. Smith ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
P120 Catenin ◽  
The Stability ◽  
E Cadherin ◽  
Cell Cell

The homeodomain transcription factors Cdx1 and Cdx2 induce E-cadherin adhesion activity by reducing β- and p120-catenin tyrosine phosphorylation

2007 ◽  
Vol 293 (1) ◽  
pp. G54-G65 ◽  
Author(s):  
Toshihiko Ezaki ◽  
Rong-Jun Guo ◽  
Hong Li ◽  
Albert B. Reynolds ◽  
John P. Lynch
Keyword(s):  
Transcription Factors ◽  
Cell Adhesion ◽  
Tyrosine Phosphorylation ◽  
Intestinal Cell ◽  
Specific Gene ◽  
P120 Catenin ◽  
Cdx2 Expression ◽  
E Cadherin ◽  
Cell Cell ◽  
Homeodomain Transcription Factors

The homeodomain transcription factors Cdx1 and Cdx2 are regulators of intestine-specific gene expression. They also regulate intestinal cell differentiation and proliferation; however, these effects are poorly understood. Previously, we have shown that expression of Cdx1 or Cdx2 in human Colo 205 cells induces a mature colonocyte morphology characterized by the induction of a polarized, columnar shape with apical microvilli and strong cell-cell adhesion. To elucidate the mechanism underlying this phenomenon, we investigated the adherens junction complex. Cdx1 or Cdx2 expression reduced Colo 205 cell migration and invasion in vitro, suggesting a physiologically significant change in cadherin function. However, Cdx expression did not significantly effect E-cadherin, α-, β-, or γ-catenin, or p120-catenin protein levels. Additionally, no alteration in their intracellular distribution was observed. Cdx expression did not alter the coprecipitation of β-catenin with E-cadherin; however, it did reduce p120-catenin-E-cadherin coprecipitation. Tyrosine phosphorylation of β- and p120-catenin is known to disrupt E-cadherin-mediated cell adhesion and is associated with robust p120-catenin/E-cadherin interactions. We specifically investigated β- and p120-catenin for tyrosine phosphorylation and found that it was significantly diminished by Cdx1 or Cdx2 expression. We restored β- and p120-catenin tyrosine phosphorylation in Cdx2-expressing cells by knocking down the expression of protein tyrosine phosphatase 1B and noted a significant decline in cell-cell adhesion. We conclude that Cdx expression in Colo 205 cells induces E-cadherin-dependent cell-cell adhesion by reducing β- and p120-catenin tyrosine phosphorylation. Ascertaining the mechanism for this novel Cdx effect may improve our understanding of the regulation of cell-cell adhesion in the colonic epithelium.

scholarly journals Early Events in Actin Cytoskeleton Dynamics and E-Cadherin-Mediated Cell-Cell Adhesion during Epithelial-Mesenchymal Transition

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 578 ◽  
Author(s):  
Irina Y. Zhitnyak ◽  
Svetlana N. Rubtsova ◽  
Nikita I. Litovka ◽  
Natalya A. Gloushankova
Keyword(s):  
Cell Adhesion ◽  
Epithelial Mesenchymal Transition ◽  
Immunofluorescent Staining ◽  
Actin Binding ◽  
Mesenchymal Transition ◽  
Actin Bundle ◽  
Cell Contacts ◽  
The Stability ◽  
E Cadherin ◽  
Cell Cell

Epithelial-mesenchymal transition (EMT) plays an important role in development and also in initiation of metastasis during cancer. Disruption of cell-cell contacts during EMT allowing cells to detach from and migrate away from their neighbors remains poorly understood. Using immunofluorescent staining and live-cell imaging, we analyzed early events during EMT induced by epidermal growth factor (EGF) in IAR-20 normal epithelial cells. Control cells demonstrated stable adherens junctions (AJs) and robust contact paralysis, whereas addition of EGF caused rapid dynamic changes at the cell-cell boundaries: fragmentation of the circumferential actin bundle, assembly of actin network in lamellipodia, and retrograde flow. Simultaneously, an actin-binding protein EPLIN was phosphorylated, which may have decreased the stability of the circumferential actin bundle. Addition of EGF caused gradual replacement of linear E-cadherin–based AJs with dynamic and unstable punctate AJs, which, unlike linear AJs, colocalized with the mechanosensitive protein zyxin, confirming generation of centripetal force at the sites of cell-cell contacts during EMT. Our data show that early EMT promotes heightened dynamics at the cell-cell boundaries—replacement of stable AJs and actin structures with dynamic ones—which results in overall weakening of cell-cell adhesion, thus priming the cells for front-rear polarization and eventual migration.

scholarly journals Downregulation of Rap1GAP in Human Tumor Cells Alters Cell/Matrix and Cell/Cell Adhesion

2010 ◽  
Vol 30 (13) ◽  
pp. 3262-3274 ◽  
Author(s):  
Oxana M. Tsygankova ◽  
Changqing Ma ◽  
Waixing Tang ◽  
Christopher Korch ◽  
Michael D. Feldman ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Tumor Cells ◽  
Adherens Junction ◽  
Protein Distribution ◽  
P120 Catenin ◽  
Cell Contacts ◽  
Cell Matrix ◽  
Junction Protein ◽  
E Cadherin ◽  
Cell Cell

ABSTRACT Rap1GAP expression is decreased in human tumors. The significance of its downregulation is unknown. We show that Rap1GAP expression is decreased in primary colorectal carcinomas. To elucidate the advantages conferred on tumor cells by loss of Rap1GAP, Rap1GAP expression was silenced in human colon carcinoma cells. Suppressing Rap1GAP induced profound alterations in cell adhesion. Rap1GAP-depleted cells exhibited defects in cell/cell adhesion that included an aberrant distribution of adherens junction proteins. Depletion of Rap1GAP enhanced adhesion and spreading on collagen. Silencing of Rap expression normalized spreading and restored E-cadherin, β-catenin, and p120-catenin to cell/cell contacts, indicating that unrestrained Rap activity underlies the alterations in cell adhesion. The defects in adherens junction protein distribution required integrin signaling as E-cadherin and p120-catenin were restored at cell/cell contacts when cells were plated on poly-l-lysine. Unexpectedly, Src activity was increased in Rap1GAP-depleted cells. Inhibition of Src impaired spreading and restored E-cadherin at cell/cell contacts. These findings provide the first evidence that Rap1GAP contributes to cell/cell adhesion and highlight a role for Rap1GAP in regulating cell/matrix and cell/cell adhesion. The frequent downregulation of Rap1GAP in epithelial tumors where alterations in cell/cell and cell/matrix adhesion are early steps in tumor dissemination supports a role for Rap1GAP depletion in tumor progression.

scholarly journals APC regulation of ESRP1 and p120-catenin isoforms in colorectal cancer cells

2020 ◽  
pp. mbc.E20-05-0321
Author(s):  
Maree C. Faux ◽  
Lauren E. King ◽  
Serena R. Kane ◽  
Christopher Love ◽  
Oliver M. Sieber ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Adhesion ◽  
Wnt Signaling ◽  
Cancer Cells ◽  
Full Length ◽  
P120 Catenin ◽  
Colorectal Cancer Cells ◽  
Isoform Switching ◽  
E Cadherin ◽  
Cell Cell

The APC tumor suppressor protein is associated with the regulation of Wnt signaling, however APC also controls other cellular processes including the regulation of cell adhesion and migration. The expression of full-length APC in SW480 colorectal cancer cells (SW480+APC) not only reduces Wnt signaling, but increases membrane E-cadherin and restores cell-cell adhesion. This report describes the effects of full-length, wild-type APC (fl-APC) on cell-cell adhesion genes and p120-catenin isoform switching in SW480 colon cancer cells: fl-APC increased the expression of genes implicated in cell-cell adhesion, whereas the expression of negative regulators of E-cadherin were decreased. Analysis of cell-cell adhesion-related proteins in SW480+APC cells revealed an increase in p120-catenin isoform 3A; similarly, depletion of APC altered the p120-catenin protein isoform profile. Expression of ESRP1 (epithelial splice regulatory protein 1) is increased in SW480+APC cells and its depletion results in reversion to the p120-catenin isoform 1A phenotype and reduced cell-cell adhesion. ESRP1 transcript is reduced in primary CRC and its expression correlates with the level of APC. Pyrvinium pamoate, which inhibits Wnt signaling, promotes ESRP1 expression. We conclude that re-expression of APC restores cell-cell adhesion gene and post-transcriptional regulatory programs leading to p120-catenin isoform switching and associated changes in cell-cell adhesion.

scholarly journals DDR1 triggers epithelial cell differentiation by promoting cell adhesion through stabilization of E-cadherin

2011 ◽  
Vol 22 (7) ◽  
pp. 940-953 ◽  
Author(s):  
Yi-Chun Yeh ◽  
Chia-Ching Wu ◽  
Yang-Kao Wang ◽  
Ming-Jer Tang
Keyword(s):  
Cell Adhesion ◽  
Underlying Mechanism ◽  
Dominant Negative ◽  
Cell Junctions ◽  
Dominant Negative Mutant ◽  
Protein Levels ◽  
Epithelial Plasticity ◽  
The Stability ◽  
E Cadherin ◽  
Cell Cell

Discoidin domain receptor 1 (DDR1) promotes E-cadherin–mediated adhesion. The underlying mechanism and its significance, however, have not been elucidated. Here we show that DDR1 overexpression augmented, whereas dominant negative mutant (DN-DDR1) or knockdown of DDR1 inhibited E-cadherin localized in cell-cell junctions in epithelial cells. DDR1 changed the localization and abundance of E-cadherin, as well as epithelial plasticity, as manifested by enhancement of microvilli formation and alteration of cytoskeletal organization. DDR1 also reduced protein abundance of mesenchymal markers, whereas DN-DDR1 and sh-DDR1 showed opposite effects. These results suggest that expression of DDR1 increases epithelial plasticity. Expression of DDR1 augmented E-cadherin protein levels by decreasing its degradation rate. Photobleaching and photoconversion of E-cadherin conjugated with Eos fluorescence protein demonstrated that DDR1 increased the stability of E-cadherin on the cell membrane, whereas sh-DDR1 decreased it. Pull-down assay and expression of constitutively active or dominant-negative Cdc42 showed that DDR1 stabilized E-cadherin through inactivation of Cdc42. Altogether, our results show that DDR1 promotes cell-cell adhesion and differentiation through stabilization of E-cadherin, which is mediated by Cdc42 inactivation.

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

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

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

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
Sign in / Sign up

Export Citation Format

Share Document