Phosphorylation and Free Pool of β-Catenin Are Regulated by Tyrosine Kinases and Tyrosine Phosphatases during Epithelial Cell Migration

Müller, Thomas; Choidas, Axel; Ernst, Rolf; Ullrich, Axel

doi:10.1074/jbc.274.15.10173

Cited by 265 publications

(218 citation statements)

References 72 publications

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“…40 The ET-18-OMe-induced loss of cell-cell adhesion might be explained through changes in association between E-cadherin and the catenins or to alterations in phosphorylation of ␤-catenin. 42 We did not find evidence for changes in phosphorylation of ␤-catenin or in the association between E-cadherin and the catenins. The latter is at variance with the finding that episialin associates with ␤-catenin in invasive breast cancer.…”

Section: Discussioncontrasting

confidence: 57%

Alkyl-lysophospholipid 1-O-octadecyl-2-O-methyl- glycerophosphocholine induces invasion through episialin-mediated neutralization of E-cadherin in human mammary MCF-7 cellsin vitro

et al. 2001

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1-O-octadecyl-2-O-methyl-glycerophosphocholine (ET-18 Key words: alkyl-lysophospholipid; E-cadherin; episialin; adhesion; invasion1-O-octadecyl-2-O-methyl-glycerophosphocholine (ET-18-OMe) interacts with cell membranes, thereby modulating phospholipid metabolism, interfering with signal transduction, inducing apoptosis and differentiation and regulating invasion. 1 On solid substrate, the E-cadherin/catenin complex is implicated in the cell-cell adhesion of 2 variants of the MCF-7 human breast cancer cell line family, coined MCF-7/AZ and MCF-7/6. In suspension, however, MCF-7/6 cells are adhesion-deficient while MCF-7/AZ cells are adhesion-proficient. Treatment with ET-18-OMe caused antithetic effects on the 2 types of MCF-7 cells. ET-18-OMe restored the E-cadherin function in the adhesiondeficient MCF-7/6 cells, whereas it caused a decrease in cellular aggregation of the adhesion-proficient MCF-7/AZ cells. The latter effects could not be explained by changes in sialylation of Ecadherin. 2 Antithetic effects on invasion have also been reported: ET-18-OMe inhibited invasion of constitutively invasive cells, [3][4][5][6] whereas it induced invasion of otherwise noninvasive cells. 7,8 Inhibition of invasion in the presence of ET-18-OMe was explained by induction of host tissue resistance, 9 but the antithetic effects on cell-cell adhesion and the invasion-promoting effect of ET-18-OMe have not been explained.Adhesion and invasion are the result of a balance between promoter and suppressor molecules modulated by multiple intraand extracellular factors. The presence of the anti-adhesion molecule episialin on the 2 types of MCF-7 cells was observed in a previous study. 2 The aim of our study was to see whether ET-18-OMe affects invasion and adhesion through modulation of episialin and E-cadherin.Episialin is a heterodimeric molecule composed of a membrane anchor and an extracellular moiety. The membrane anchor consists of a cytoplasmatic domain of 68 amino acids and a transmembrane domain. The extracellular moiety consists of a large mucin domain containing a large number of O-linked glycans. 10 The carbohydrate side chains carry many sialic acid residues conveying a highly negative charge upon episialin. 11 Episialin is located at the apical surface of most glandular epithelial cells; it is over-expressed in carcinomas, often distributed over the entire cell surface. 11 Overexpression of episialin inhibits integrin-mediated cell adhesion to

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Section: Discussioncontrasting

confidence: 57%

Alkyl-lysophospholipid 1-O-octadecyl-2-O-methyl- glycerophosphocholine induces invasion through episialin-mediated neutralization of E-cadherin in human mammary MCF-7 cellsin vitro

et al. 2001

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“…On the other hand, b-catenin belongs to structural proteins like the other catenins and the cadherins. By constituting the cell-adhesion complex, these proteins are responsible for cell-cell adhesion and more complex processes such as cellular motility (Liu et al, 1997;MuÈ ller et al, 1999). Therefore, we investigated whether interfering with the Wnt pathway by ectopic expression of the soluble sFRPs would lead to a modulation of cellular motility.…”

Section: Discussionmentioning

confidence: 99%

“…Instead, free b-catenin translocates to the nucleus where it serves as a transactivator for the transcription factor T-cell factor (TCF), leading to the transcription of several target genes. On the other hand, a change in the rheostat of complex-bound, cytoplasmic, and free, uncomplexed b-catenin also a ects its role as a structural protein in the cell adhesion complexes (MuÈ ller et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

Secreted Frizzled-related proteins inhibit motility and promote growth of human malignant glioma cells

et al. 2000

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Cellular resistance to multiple proapoptotic stimuli and invasion of surrounding brain tissue by migrating tumor cells are main obstacles to an e ective therapy for human malignant glioma. Here, we report that the Wnt family of embryonic di erentiation genes modulate growth of malignant glioma cells in vitro and in vivo and inhibit cellular migration in vitro. sFRPs (soluble Frizzled-related proteins) are soluble proteins that bind to Wnt and interfere with Wnt signaling. We ®nd that sFRP-1 and sFRP-2 are produced by the majority of longterm and ex vivo malignant glioma cell lines. Glioma cells that ectopically express sFRPs exhibit increased clonogenicity and enhanced resistance to serum starvation. In contrast, sFRPs do not modulate glioma cell susceptibility to apoptosis induced by the cytotoxic cytokines, CD95 (Fas/APO-1) ligand (CD95L) or Apo2 ligand/tumor necrosis factor-related apoptosisinducing ligand (Apo2L/TRAIL), or various cytotoxic drugs. sFRP-2 strongly promotes the growth of intracranial glioma xenografts in nude mice. In contrast, enhanced expression of sFRPs inhibits the motility of glioma cells in vitro. sFRP-mediated e ects on glioma cells are accompanied by decreased expression and activity of matrix metalloproteinase-2 (MMP-2) and decreased tyrosine phosphorylation of b-catenin. Thus, sFRPs promote survival under non-supportive conditions and inhibit the migration of glioma cells. We suggest that the regulation of these cellular processes involves expression of MMP-2 and tyrosine phosphorylation of bcatenin. These data support a function for Wnt signaling and its modulation by sFRPs in the biology of human gliomas. Oncogene (2000) 19, 4210 ± 4220.

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“…LAR-PTP (Kypta et al, 1996;Mü ller et al, 1999) has been shown to interact with and dephosphorylate ␤-catenin. Additionally, overexpression of LAR-PTP correlates with prevention of ␤-catenin phosphorylation and inhibition of epithelial cell migration (Mü ller et al, 1999).…”

Section: Destabilizing Adhesions: Altering the Balance Between Phosphmentioning

confidence: 99%

“…Additionally, overexpression of LAR-PTP correlates with prevention of ␤-catenin phosphorylation and inhibition of epithelial cell migration (Mü ller et al, 1999). Similarly, PTP␤/ interacts with and dephosphorylates ␤-catenin (Meng et al, 2000).…”

Section: Destabilizing Adhesions: Altering the Balance Between Phosphmentioning

confidence: 99%

Turn‐off, drop‐out: Functional state switching of cadherins

Lilien

Balsamo

Arregui

et al. 2002

Developmental Dynamics

147

116

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The classic cadherins are a group of calcium dependent, homophilic cell-cell adhesion molecules that drive morphogenetic rearrangements and maintain the integrity of cell groups through the formation of adherens junctions. The formation and maintenance of cadherin-mediated adhesions is a multistep process and mechanisms have evolved to regulate each step. This suggests that functional state switching plays an important role in development. Among the many challenges ahead is to determine the developmental role that functional state switching plays in tissue morphogenesis and to define the roles of each of the several regulatory interactions that participate in switching. One correlate of the loss of cadherinmediated adhesion, the "turn-off" of cadherin function, is the exit, or "drop-out" of cells from neural and epithelial layers and their conversion to a motile phenotype. We suggest that epithelial mesenchymal conversions may be initiated by signaling pathways that result in the loss of cadherin function. Tyrosine phosphorylation of ␤-catenin is one such mechanism. Enhanced phosphorylation of tyrosine residues on ␤-catenin is almost invariably associated with loss of the cadherin-actin connection concomitant with loss of adhesive function. There are several tyrosine kinases and phosphatases that have been shown to have the potential to alter the phosphorylation state of ␤-catenin and thus the function of cadherins. Our laboratory has focused on the role of the nonreceptor tyrosine phosphatase PTP1B in regulating the phosphorylation of ␤-catenin on tyrosine residues. Our data suggest that PTP1B is crucial for maintenance of N-cadherin-mediated adhesions in embryonic neural retina cells. By using an L-cell model system constitutively expressing N-cadherin, we have worked out many of the molecular interactions essential for this regulatory interaction. Extracellular cues that bias this critical regulatory interaction toward increased phosphorylation of ␤-catenin may be a critical component of many developmental events.

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Phosphorylation and Free Pool of β-Catenin Are Regulated by Tyrosine Kinases and Tyrosine Phosphatases during Epithelial Cell Migration

Cited by 265 publications

References 72 publications

Alkyl-lysophospholipid 1-O-octadecyl-2-O-methyl- glycerophosphocholine induces invasion through episialin-mediated neutralization of E-cadherin in human mammary MCF-7 cellsin vitro

Alkyl-lysophospholipid 1-O-octadecyl-2-O-methyl- glycerophosphocholine induces invasion through episialin-mediated neutralization of E-cadherin in human mammary MCF-7 cellsin vitro

Secreted Frizzled-related proteins inhibit motility and promote growth of human malignant glioma cells

Turn‐off, drop‐out: Functional state switching of cadherins

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