Dominant-negative E-cadherin alters adhesion and reverses contact inhibition of growth in breast carcinoma cells

Vizirianakis, Ioannis S.; Chen, Yaoqi; Kantak, Seema S.; Tsiftsoglou, Asterios S.; Kramer, Randall H.

doi:10.3892/ijo.21.1.135

Cited by 21 publications

(28 citation statements)

References 39 publications

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“…Tight junction-associated proteins, ZO-1 and occludin were also localized to the cell periphery. Together, the ultrastructure and IF analysis of MCF-7 cells showed stable junctions, as seen previously (van Deurs et al, 1987;Sommers et al, 1994;Mauro et al, 2001;Zhu et al, 2001;Vizirianakis et al, 2002).…”

Section: Subcellular Distribution Of Junctional Proteins In Mcf-7 Andsupporting

confidence: 85%

Bcl-2 expression decreases cadherin-mediated cell-cell adhesion

Backer

Wong

et al. 2003

Journal of Cell Science

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Bcl-2, a member of the apoptosis-regulating family of proteins confers a survival advantage on cells by inhibiting apoptosis. Bcl-2 expression is estrogen-responsive and high in various tumors. Overexpression of Bcl-2 has been associated with the loss of contact inhibition, unregulated growth and foci formation in culture. In this study, we have examined the effects of bcl-2 overexpression and expression on cell-cell adhesion in MCF-7 and MDCK epithelial cell lines respectively. Overexpression of Bcl-2 in estrogen receptor-positive MCF-7 mammary carcinoma cells led to decreased cell surface E-cadherin and the disruption of junctional complexes concurrent with intracellular redistribution of their components. Particularly noticeable, was the partial nuclear localization of the tight junction-associated protein ZO-1 which coincided with upregulation of ErbB2. The expression of this EGF co-receptor is regulated by the ZO-1-associated transcription factor ZONAB. Growth in estrogen-depleted media led to downregulation of Bcl-2 expression and upregulation and membrane localization of all junctional proteins. Similar disruption in junctions, accompanied by decreased transepithelial resistance, was observed when Bcl-2 was expressed in MDCK cells. These results strongly suggest that Bcl-2 expression decreases the level of functional E-cadherin thereby interfering with junction formation. The inhibition of junction formation decreases cell-cell adhesion leading to the loss of contact inhibition, which, in vivo, can lead to unregulated growth and tumorigenesis.

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Section: Subcellular Distribution Of Junctional Proteins In Mcf-7 Andsupporting

confidence: 85%

Bcl-2 expression decreases cadherin-mediated cell-cell adhesion

Backer

Wong

et al. 2003

Journal of Cell Science

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“…Gadd45a induction upregulated b-catenin and the disruption of endogenous Gadd45a resulted in b-catenin downregulation. b-Catenin is a central player in CCA and its downregulation can lead to the disruption of CCA/CCI and cell malignancy (Vizirianakis et al, 2002;Kudo et al, 2004). In addition, b-catenin is a key component of the Wnt signal transduction pathway and activation of Wnt signaling leads to the nuclear translocation of b-catenin, which induces gene transcription such as cyclin D1 and contributes to cell malignancy (Cadigan and Nusse, 1997).…”

Section: Gadd45a Gene Was Initially Isolated From Chinesementioning

confidence: 99%

“…The loss of cell contact inhibition (CCI) and cell-cell adhesion (CCA) results in cell malignant transformation (Vizirianakis et al, 2002;Kudo et al, 2004;Salon et al, 2004;Kato et al, 2005). Cadherins are implicated in this process and specifically locate at intercellular adhesion junctions (Gottardi and Gumbiner, 2001).…”

Section: Introductionmentioning

confidence: 99%

“…b-Catenin is also essential for CCA and CCI by linking cadherins to the actin cytoskeleton through its interaction with the intracellular tail of cadherins (Kemler, 1993;Gumbiner, 2000;Dietrich et al, 2002). The loss of cadherin/ b-catenin complex function leads to the disruption of CCI and CCA, which is important for cell malignancy and cell invasion (Vizirianakis et al, 2002;Kudo et al, 2004;Salon et al, 2004;Kato et al, 2005). Therefore, cadherins/b-catenin complexes, CCA complexes, are important in suppressing tumor progression.…”

Section: Introductionmentioning

confidence: 99%

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Gadd45a regulates β-catenin distribution and maintains cell–cell adhesion/contact

Liu

Tong

et al. 2007

Oncogene

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Gadd45a, a growth arrest and DNA-damage gene, plays important roles in the control of cell cycle checkpoints, DNA repair and apoptosis. We show here that Gadd45a is involved in the control of cell contact inhibition and cellcell adhesion. Gadd45a can serve as an adapter to enhance the interaction between b-catenin and Caveolin-1, and in turn induces b-catenin translocation to cell membrane for maintaining cell-cell adhesion/contact inhibition. This is coupled with reduction of b-catenin in cytoplasm and nucleus following Gadd45a induction, which is reflected by the downregulation of cyclin D1, one of the b-catenin targeted genes. Additionally, Gadd45a facilitates ultraviolet radiation-induced degradation of cytoplasmic and nuclear b-catenin in a p53-dependent manner via activation of p38 kinase. These findings define a novel link that connects Gadd45a to cell-cell adhesion and cell contact inhibition, which might contribute to the role of Gadd45a in inhibiting tumorigenesis.

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“…H2kd-E-cadherin is a chimeric protein composed of the extracellular domain of the murine MHC class I antigen H2kd fused to the cytoplasmic and transmembrane domains of E-cadherin (16 amino acids of the extracellular domain of E-cadherin are also present). H2kd-Ecadherin has been shown to decrease endogenous levels of E-cadherin, increase protein levels of β-catenin and increase β-catenin signaling (Vizirianakis et al, 2002;Zhu and Watt, 1996). As ES cells undergo several rounds of mitosis during the process of differentiation in vitro, stably transfected cell lines were established to avoid possible effects due to dilution of transiently transfected cells and/or preferential proliferation of nontransfected cells.…”

Section: Generation Of Stable Cell Linesmentioning

confidence: 99%

β-Catenin signaling is required for neural differentiation of embryonic stem cells

et al. 2004

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Culture of embryonic stem (ES) cells at high density inhibits bothβ-catenin signaling and neural differentiation. ES cell density does not influence β-catenin expression, but a greater proportion ofβ-catenin is targeted for degradation in high-density cultures. Moreover,in high-density cultures, β-catenin is preferentially localized to the membrane further reducing β-catenin signaling. Increasing β-catenin signaling by treatment with Wnt3a-conditioned medium, by overexpression ofβ-catenin, or by overexpression of a dominant-negative form of E-cadherin promotes neurogenesis. Furthermore, β-catenin signaling is sufficient to induce neurogenesis in high-density cultures even in the absence of retinoic acid (RA), although RA potentiates the effects of β-catenin. By contrast,RA does not induce neurogenesis in high-density cultures in the absence ofβ-catenin signaling. Truncation of the armadillo domain ofβ-catenin, but not the C terminus or the N terminus, eliminates its proneural effects. The proneural effects of β-catenin reflect enhanced lineage commitment rather than proliferation of neural progenitor cells. Neurons induced by β-catenin overexpression either alone or in association with RA express the caudal neuronal marker Hoxc4. However, RA treatment inhibits the β-catenin-mediated generation of tyrosine hydroxylase-positive neurons, suggesting that not all of the effects of RA are dependent upon β-catenin signaling. These observations suggest thatβ-catenin signaling promotes neural lineage commitment by ES cells, and that β-catenin signaling may be a necessary co-factor for RA-mediated neuronal differentiation. Further, enhancement of β-catenin signaling with RA treatment significantly increases the numbers of neurons generated from ES cells, thus suggesting a method for obtaining large numbers of neural species for possible use in for ES cell transplantation.

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Dominant-negative E-cadherin alters adhesion and reverses contact inhibition of growth in breast carcinoma cells

Cited by 21 publications

References 39 publications

Bcl-2 expression decreases cadherin-mediated cell-cell adhesion

Bcl-2 expression decreases cadherin-mediated cell-cell adhesion

Gadd45a regulates β-catenin distribution and maintains cell–cell adhesion/contact

β-Catenin signaling is required for neural differentiation of embryonic stem cells

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