From cadherins to catenins: cytoplasmic protein interactions and regulation of cell adhesion

Kemler, Rolf

doi:10.1016/0168-9525(93)90250-l

Cited by 932 publications

(676 citation statements)

References 38 publications

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“…The biological consequences of homozygosity for M i n can be compared with a deficiency of E-cadherin, which also interacts with the catenins and is expressed as early as the morula stage in the embryo (Takeichi, 1990;Kemler et al, 1993). Embryos homozygous for a targeted E-cadherin mutation show no effects on cell viability but fail to establish an epithelial architecture of the trophectoderm (Larue et al, 1994).…”

Section: Discussionmentioning

confidence: 99%

Homozygosity for theMinallele ofApcresults in disruption of mouse development prior to gastrulation

Moser

Shoemaker

Connelly

et al. 1995

Developmental Dynamics

144

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Section: Discussionmentioning

confidence: 99%

Homozygosity for theMinallele ofApcresults in disruption of mouse development prior to gastrulation

Moser

Shoemaker

Connelly

et al. 1995

Developmental Dynamics

144

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“…E-cadherin is a tumor suppressor protein whose loss is thought to promote tumor growth and invasion by a mechanism involving b-catenin (Wong and Gumbiner, 2003). b-Catenin was originally identified as a cytoplasmic component of adherens junctions, in which it associates with E-cadherin and, via a-catenin, the actin cytoskeleton (Kemler, 1993;Geiger et al, 1995). In addition, b-catenin is the main effector of Wnt signaling in the nucleus, in which it interacts with lymphoid enhancer factor/T-cell factor (LEF/TCF) transcription factors to regulate the expression of genes involved in cell growth control, such as cyclin D1 (van Noort and Clevers, 2002;Conacci-Sorrell et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

E-cadherin inhibits tumor cell growth by suppressing PI3K/Akt signaling via β-catenin-Egr1-mediated PTEN expression

2011

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E-cadherin is a cell-cell adhesion protein and tumor suppressor that is silenced in many malignancies. E-cadherin is thought to suppress tumor cell growth by antagonizing b-catenin signaling. However, the role of E-cadherin in ovarian cancer progression is still controversial. In this study, we showed that loss of E-cadherin induced ovarian cancer cell growth and constitutive activation of phosphoinositide 3-kinase (PI3K)/Akt signaling by the inhibition of phosphatase and tensin homolog (PTEN) transcription through the downregulation of early growth response gene 1 (Egr1). In addition, immunofluorescence microscopy and T-cell factor promoter/luciferase reporter assays showed that E-cadherin loss was associated with enhanced nuclear b-catenin signaling. Constitutive activation of PI3K/Akt signaling reinforced nuclear b-catenin signaling by inactivating glycogen synthase kinase-3b indicating cross-talk between the PI3K/Akt and b-catenin signaling pathways. Finally, we found that E-cadherin negatively regulates tumor cell growth, in part, by positively regulating PTEN expression via b-catenin-mediated Egr1 regulation, thus influencing PI3K/Akt signaling. In summary, endogenous E-cadherin inhibits PI3K/Akt signaling by antagonizing b-catenin-Egr1-mediated repression of PTEN expression. Thus, the loss of E-cadherin itself may contribute to dysregulated PI3K/Akt signaling through its effects on PTEN, or it may exacerbate the frequent activation of PI3K/Akt signaling that occurs as a result of overexpression, mutation and/or amplification.

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“…This protein plays a major role in cell adhesion, where it is associated with the cadherins, a family of transmembrane cell adhesion molecules (Kemler, 1993). In addition, it has been shown recently, that b-catenin associates with the transcription factor lymphocyte enhancer binding factor/T-cell factor (LEF/TCF) and is translocated into the nucleus, where it is able to regulate gene transcription (Behrens et al, 1996;He et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

The Adenomatous Polyposis Coli-protein (APC) interacts with the protein tyrosine phosphatase PTP-BL via an alternatively spliced PDZ domain

Erdmann

Kuhlmann²,

Leßmann

et al. 2000

Oncogene

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Mutations of the tumor suppressor protein APC (Adenomatous Polyposis Coli) are linked to familiar and sporadic human colon cancer. Here we describe a novel interaction between the APC protein and the protein tyrosine phosphatase PTP-BL carrying ®ve PDZ protein ± protein interaction domains. Exclusively, the second PDZ domain (PDZ2) of PTP-BL is binding to the extreme C-terminus of the APC protein, as determined by yeast two-hybrid studies. Using surface plasmon resonance analysis we established a dissociation constant (K D ) of 8.1610 79 M. We ®nd that a naturally occurring splice insertion of ®ve amino acids (PDZ2b) abolishes its binding a nity to the APC protein. The in vivo interaction between PTP-BL and the APC protein was shown by coprecipitation experiments in transfected COS cells. Furthermore, in cultured epithelial Madine Carnine Kidney cells the subcellular colocalization was demonstrated for the nucleus and also for the tips of cellular extensions. The interaction of the APC protein with a protein tyrosine phosphatase may indirectly modulate the steady state levels of tyrosine phosphorylations of associated proteins, such as b-catenin playing a major role in the regulation of cell division, migration and cell adhesion. Oncogene (2000) 19, 3894 ± 3901.

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From cadherins to catenins: cytoplasmic protein interactions and regulation of cell adhesion

Cited by 932 publications

References 38 publications

Homozygosity for theMinallele ofApcresults in disruption of mouse development prior to gastrulation

Homozygosity for theMinallele ofApcresults in disruption of mouse development prior to gastrulation

E-cadherin inhibits tumor cell growth by suppressing PI3K/Akt signaling via β-catenin-Egr1-mediated PTEN expression

The Adenomatous Polyposis Coli-protein (APC) interacts with the protein tyrosine phosphatase PTP-BL via an alternatively spliced PDZ domain

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