Beta-catenin stabilization extends regulatory T cell survival and induces anergy in nonregulatory T cells

Ding, Yi; Shen, Shiqian; Lino, Andreia C.; Lafaille, Maria A. Curotto de; Lafaille, Juan J.

doi:10.1038/nm1707

Cited by 178 publications

(197 citation statements)

References 38 publications

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“…These results are reminiscent of the observation made recently that b-catenin plays an important and complex role in the biology of normal mouse T cells. 15 Our results also uncovered a cross-talk between b-catenin and STAT3 in ALK since the level of reduction at the mRNA level was similar to that seen at the protein level. This conclusion is in keeping with the previous report that the STAT3 promoter contains multiple TCF binding sites.…”

Section: Y654supporting

confidence: 71%

“…12,14 b-catenin has been recently shown to play a role in the survival and proliferation of normal murine CD4 + T cells. 15 In benign human lymphocytes, the expression level of b-catenin is regulated through a posttranslational mechanism. Specifically, this protein is continuously degraded in normal resting peripheral blood lymphocytes, 16 such that b-catenin is undetectable by western blot studies.…”

Section: Introductionmentioning

confidence: 99%

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-catenin is constitutively active and increases STAT3 expression/activation in anaplastic lymphoma kinase-positive anaplastic large cell lymphoma

Anand¹,

Lai²,

Gélébart³

2010

Haematologica

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The online version of this article has a Supplementary Appendix. BackgroundThe role of b-catenin in cancer has been most studied in tumors of epithelial cell origin. The functional status and biological significance of this protein in anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma is unknown. Design and MethodsALK-positive anaplastic large cell lymphoma cell lines and patients' tumor samples were examined for status of b-catenin expression and signaling. The subcellular localization of b-catenin was assessed using immunohistochemistry, sub-cellular fractionation and confocal microscopy, while its transcriptional activity was studied using the TOPFlash/FOPFlash luciferase reporter assay. To examine the biological significance of b-catenin, short interfering RNA was used to knock-down its expression; the resulting biological effects were studied using trypan-blue exclusion and MTS assay, and the impact on its various downstream targets was assessed using quantitative real-time polymerase chain reaction and western blots. Resultsb-catenin was transcriptionally active in three of three ALK-positive anaplastic large cell lymphoma cell lines, and this finding correlates with the nuclear localization of b-catenin in these cells and the neoplastic cells identified in most of the patients' tumor samples. b-catenin is biologically significant in ALK-positive anaplastic large cell lymphoma, since down-regulation of b-catenin resulted in a significant reduction in their cell growth. Down-regulation of b-catenin led to a marked reduction in both the total protein level and the activated/phosphorylated form of STAT3, another signaling protein previously shown to be important in the pathogenesis of ALK-positive anaplastic large cell lymphoma. In contrast to some of the oncogenic tyrosine kinases, modulation of nucleophosmin-anaplastic lymphoma kinase expression did not result in any detectable change in the protein level, nuclear localization or tyrosine phosphorylation of b-catenin; however, inhibition of nucleophosmin-anaplastic lymphoma kinase expression significantly down-regulated the transcriptional activity of b-catenin. Conclusionsb-catenin signaling is constitutively active in ALK-positive anaplastic large cell lymphoma and represents a previously unknown mechanism by which the high levels of STAT3 expression and activation in these tumors are sustained. Our results suggest that the interaction between oncogenic tyrosine kinases and various cell signaling proteins may be more complex than previously believed.

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Section: Y654supporting

confidence: 71%

Section: Introductionmentioning

confidence: 99%

-catenin is constitutively active and increases STAT3 expression/activation in anaplastic lymphoma kinase-positive anaplastic large cell lymphoma

Anand¹,

Lai²,

Gélébart³

2010

Haematologica

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“…In addition, GSK-3␤ exerts indirect regulatory control of Foxp3 via ␤-catenin and Bcl-xL so that treating Treg cells with a GSK-3␤ inhibitor prolonged the half-life of Foxp3 protein and increased the levels of Bcl-xL (31). Stabilization of ␤-catenin has been proven to improve Treg cell survival (32). Taken together, these findings indicate that GSK-3␤ plays a vital role in the regulation of Foxp3 protein expression.…”

Section: Discussionmentioning

confidence: 91%

Amphiregulin Confers Regulatory T Cell Suppressive Function and Tumor Invasion via the EGFR/GSK-3β/Foxp3 Axis

Wang¹,

Zhang²,

Wang

et al. 2016

Journal of Biological Chemistry

112

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“…Indeed, stabilization of β-catenin in murine Treg supports their survival and their suppressive capacity. 46 In addition, stable β-catenin expression in effector T cells induces anergy and prevents inflammatory responses. 46 Treatment of polyclonal stimulated human T cells with either Wnt3a or a GSK-3β inhibitor prevented polarization of these cells.…”

Section: Dendritic Cellsmentioning

confidence: 99%

“…46 In addition, stable β-catenin expression in effector T cells induces anergy and prevents inflammatory responses. 46 Treatment of polyclonal stimulated human T cells with either Wnt3a or a GSK-3β inhibitor prevented polarization of these cells. 47 Moreover, blocking of GSK-3β reduces proliferation and cytokine secretion.…”

Section: Dendritic Cellsmentioning

confidence: 99%

Take the Wnt out of the inflammatory sails: modulatory effects of Wnt in airway diseases

Reuter

Beckert

Taube

2016

Laboratory Investigation

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Bronchial asthma and chronic obstructive pulmonary disease (COPD) are chronic diseases that are associated with inflammation and structural changes in the airways and lungs. Recent findings have implicated Wnt pathways in critically regulating inflammatory responses, especially in asthma. Furthermore, canonical and noncanonical Wnt pathways are involved in structural changes such as airway remodeling, goblet cell metaplasia, and airway smooth muscle (ASM) proliferation. In COPD, Wnt pathways are not only associated with structural changes in the airways but also involved in the development of emphysema. The present review summarizes the role and function of the canonical and noncanonical Wnt pathway with regard to airway inflammation and structural changes in asthma and COPD. Further identification of the role and function of different Wnt molecules and pathways could help to develop novel therapeutic options for these diseases.

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Beta-catenin stabilization extends regulatory T cell survival and induces anergy in nonregulatory T cells

Cited by 178 publications

References 38 publications

-catenin is constitutively active and increases STAT3 expression/activation in anaplastic lymphoma kinase-positive anaplastic large cell lymphoma

-catenin is constitutively active and increases STAT3 expression/activation in anaplastic lymphoma kinase-positive anaplastic large cell lymphoma

Amphiregulin Confers Regulatory T Cell Suppressive Function and Tumor Invasion via the EGFR/GSK-3β/Foxp3 Axis

Take the Wnt out of the inflammatory sails: modulatory effects of Wnt in airway diseases

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